The attorney general testified at a lengthy hearing Thursday before the House Judiciary Committee, where Republican members echoed calls for Holder's resignation and, in several instances, called for "heads to roll" at the top tier of the Department of Justice.
FULL COVERAGE: ATF's Fast and Furious scandal
Republican Rep. Jim Sensenbrenner of Wisconsin suggested that some political appointees at Justice should be removed immediately, and asked Holder when he was going to "clean up this mess." He added, "If you don't get to the bottom of this," the only other option might be "impeachment."
But Holder suggested that it was this kind of rhetoric that was politicizing the furor over the gun-tracking operation in which federal Bureau of Alcohol, Tobacco, Firearms and Explosives agents purposely allowed weapons to be illegally purchased and circulated on both sides of the U.S.-Mexico border.
Two of the weapons turned up after a U.S. Border Patrol agent was killed in southern Arizona a year ago, and scores of others were reportedly used in violent crimes in Mexico. While the aim of Fast and Furious was to track weapons, instead it ended up significantly arming the Mexican drug cartels.
"It is an unfortunate reality that we will continue to feel the effects of this flawed operation for years to come," Holder also warned. "Guns lost during this operation will continue to show up at crime scenes on both sides of the border."
He added in pointed language to Republicans on the panel that "as we work to avoid future losses and further mistakes, it is unfortunate that some have used inflammatory and inappropriate rhetoric about one particular tragedy that occurred near the southwest border in an effort to score political points."
Holder has maintained he was unaware of Fast and Furious until months after Agent Brian Terry's death last December and that he has since requested a Justice Department inspector general's investigation and ordered his employees never to open similar operations that include illegal gun-"walking."
Republicans have countered that he should have known much earlier, and if he did not, it suggests he is "incompetent" to continue in his post. They also have hinted that Holder might even have approved or condoned the gun-walking tactics under Fast and Furious.
The investigation was conducted by the ATF's Phoenix field office between fall 2009 and January 2011.
Under questioning by Rep. Jason Chaffetz (R-Utah), Holder conceded he has not spoken with President Obama, other Obama Cabinet members or the president of Mexico about Fast and Furious.
"You don't have 15 minutes to pick up the phone?" Chaffetz asked.
Holder said others in his department have discussed Fast and Furious with top U.S. and Mexico officials, and that he has made some "personnel changes" at ATF headquarters.
On the Democratic side, Rep. Mike Quigley (D-Ill.) said simply about Fast and Furious: "Horrible screw-up. Horrible screw-up."