Sen. Rand Paul ended his filibuster shortly after midnight, but Senate Minority Leader Mitch McConnell, also a Kentucky Republican, said he would continue to oppose Brennan's confirmation and ending debate on it.
After Paul yielded the floor, Sen. Dick Durbin, D-Ill., filed a motion to cut off debate on Brennan's nomination and bring it up for a vote.
Paul ended his lengthy speech with a joke. He said that he was tempted to go another 12 hours and try and break former South Carolina Sen. Strom Thurmond's filibuster record of 24 hours, but he needed to use the bathroom.
"I discovered that there are some limits to filibustering and I'm going to have to go and take care of one of those in a few minutes," Paul said.
But Paul's performance clearly energized his colleagues and even he seemed invigorated as the night progressed. Paul, a tea party favorite and a Republican critic of President Barack Obama's unmanned drone policy, started just before noon Wednesday by demanding the president or Attorney General Eric Holder issue a statement assuring that the aircraft would not be used in the United States to kill terrorism suspects who are U.S. citizens. He wasn't picky about the format, saying at one point he'd be happy with a telegram or a Tweet.
But by the time he left the floor, he said he'd received no response.
In a show of support, more than a dozen of Paul's colleagues who share his conservative views came to floor to take turns speaking for him and trading questions. McConnell congratulated Paul for his "tenacity and for his conviction." McConnell also called Obama's choice, John Brennan, a "controversial nominee."
Paul said he recognized that he can't stop Brennan from being confirmed. But the nomination was the right vehicle for a debate over what the Obama White House believes are the limits of the federal government's ability to conduct lethal operations against suspected terrorists, he said.
Sen. Ted Cruz, R-Texas, read Twitter messages from people eager to "Stand With Rand." The Twitterverse, said Cruz, is "blowing up." And as the night went on, Cruz spoke for longer periods as Paul leaned against a desk across the floor. Cruz, an insurgent Republican with strong tea party backing, read passages from Shakespeare's "Henry V" and lines from the 1970 movie "Patton," starring George C. Scott.
Sen. Marco Rubio, R-Fla., made references to rappers Jay-Z and Wiz Khalifa. Rubio, a possible GOP presidential candidate in 2016, chided the White House for failing to respond. "It's not a Republican question. It's not a conservative question," Rubio said. "It's a constitutional question."
Dressed in a dark suit, white shirt and red tie, Paul read from notebooks filled with articles about the expanded use of the unmanned weapons that have become the centerpiece of the Obama administration's campaign against al-Qaida suspects. As he moved about the Senate floor, aides brought him glasses of water, which he barely touched. Senate rules say a senator has to remain on the floor to continue to hold it, even though he can yield to another senator for a question.
"No president has the right to say he is judge, jury and executioner," Paul said.
Not all Republicans were so enthusiastic about Paul's performance. Sen. Lindsey Graham, R-S.C., said the prospect of drones being used to kill people in the United States was "ridiculous" and called the debate "paranoia between libertarians and the hard left that is unjustified."
Rep. Mike Rogers, R-Mich., the chairman of the House Intelligence Committee, echoed Graham. He said it is unconstitutional for the U.S. military or intelligence agencies to conduct lethal counterterrorism operations in the United States against U.S. citizens. Suggesting they can or might, Rogers said, "provokes needless fear and detracts attention from the real threats facing the country."
Later in the evening Paul, who is the son of former Texas congressman and libertarian leader Ron Paul, offered to allow a vote on Brennan if the Senate would vote on his resolution stating that the use of the unmanned, armed aircraft on U.S. soil against American citizens violates the Constitution. Democrats rejected the offer.
Along with Cruz and Wyden, Republican Sens. Mike Lee of Utah, Jerry Moran of Kansas and Marco Rubio of Florida joined Paul briefly three hours into the debate but turned it back to him. Wyden has long pressed for greater oversight of the use of drones. Sen. John Barrasso, R-Wyo., appeared later in the evening to trade questions with Paul.
The record for the longest individual speech on the Senate floor belongs to Thurmond, who filibustered for 24 hours and 18 minutes against the Civil Rights Act of 1957.
Holder came close to making the statement Paul wanted earlier in the day during an exchange with Cruz at a Senate Judiciary Committee hearing, according to Paul.
Cruz asked Holder if the Constitution allowed the federal government to kill a U.S. citizen on U.S. soil who doesn't pose an imminent threat. Holder said the situation was hypothetical, but he did not think that in that situation the use of a drone or lethal force would be appropriate. Cruz criticized Holder for not simply saying "no" in response.
In a letter sent Tuesday to Paul, Brennan said the CIA does not have authority to conduct lethal operations inside the U.S.
Holder told Paul in a March 4 letter that the federal government has not conducted such operations and has no intention of doing so. But Holder also wrote that he supposed it was possible under an "extraordinary circumstance" that the president would have no choice but to authorize the military to use lethal force inside U.S. borders. Holder cited the attacks at Pearl Harbor and on Sept. 11, 2001, as examples.
Paul said he did not dispute that the president has the authority to take swift and lethal action against an enemy that carried out a significant attack against the United States. But Paul said he was "alarmed" at how difficult it has been to get the administration to clearly define what qualifies as a legitimate target of a drone strike.
Brennan's nomination won approval Tuesday by the Senate Intelligence Committee after the White House broke a lengthy impasse by agreeing to give lawmakers access to top-secret legal opinions justifying the use of lethal drone strikes against al-Qaida suspects overseas.
If confirmed, Brennan would replace Michael Morell, the CIA's deputy director who has been acting director since David Petraeus resigned in November after acknowledging an affair with his biographer.
Brennan currently serves as Obama's top counterterrorism adviser in the White House. He was nominated for the CIA post by the president in early January and the Intelligence Committee held his confirmation hearing on Feb. 7.
Associated Press writer Jim Kuhnhenn contributed to this report.