The pro-gun amendment tacked on to a critical defense-funding bill would allow gun owners to carry concealed weapons across state lines.
Sponsors call it a crime-fighting tool.
"One of best ways to help prevent hate crimes against potential victims of hate crimes is to allow them to defend themselves," said Sen. John Thune, R-S.D., the amendment's author.
But, opponents, including 450 U.S. mayors who signed a full-page add in USA Today, say the bill, if passed, will put police and citizens in greater danger.
"This is about as anti-police, pro-gun trafficker piece of legislation that has ever come before the United States Senate," said New York Mayor Michael Bloomberg.
And opponents note the timing is terrible. Violent crime is plunging, with big-city murders nearing 30-year lows.
"It could reverse the dramatic success we've had in reducing crime in most parts of America," said Sen. Charles Schumer, D-N.Y.
Under the new law, gun buyers could obtain for permits in states with weak regulations and then carry the weapons, unchecked, virtually anywhere.
But the National Rifle Association argues the right of self-defense should not stop at the state line, a point that resonates with conservatives and Democrats from pro-gun states.
Opponents are still trying to find a way to kill the gun measure without putting defense funding in jeopardy. But, the Senate's top Democrat says he's ready to pass it when the roll is called tomorrow.