"I have decided that my law enforcement background better qualifies me for a race for New York State attorney general than a race for the United States Senate," Pirro, the Westchester County district attorney, said in a statement.
With her campaign against Clinton in trouble, Pirro had been under strong pressure from top state GOP leaders to make the switch.
The move leaves Republicans with two active candidates for the Senate nomination: former Yonkers Mayor John Spencer, who is not well known statewide, and an even less well known tax attorney from the Catskills region, William Brenner.
Some supporters expect New York City lawyer Edward Cox, a son-in-law of President Nixon, to consider re-entering the Senate race. Cox withdrew in October after Republican Gov. George Pataki endorsed Pirro.
But Pirro has had trouble raising money, and independent polls have shown the former first lady, a potential 2008 presidential contender, with huge leads over Pirro and the other potential GOP challengers. As of the end of September, Clinton had about $14 million in her campaign coffers.
Pirro, a supporter of abortion and gay rights, also had major problems in her attempts to court support from leaders of the state Conservative Party. No Republican running statewide in New York has won without Conservative Party support since 1974.
Michael Long, the Conservative Party state chairman, said he had always urged Pirro to run for attorney general rather than the Senate.