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.