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WASHINGTON — A major test of how carefully Republicans can navigate the perilous intraparty politics of sexuality will come Monday, when the Senate holds a crucial vote on a bill to outlaw workplace discrimination against gay men, lesbians and transgender people.

Four months after the Supreme Court invalidated a federal ban on recognizing same-sex marriages, and nearly a year after some conservatives warned that their 2012 losses exposed the party as out of touch with much of the country on social issues, the vote will mark the first time since that Republicans have faced a question of gay rights at the federal level.

They are proceeding cautiously. With the bill apparently just one vote short of the threshold to prevent a filibuster, the Republican senators believed to be the most persuadable — Rob Portman of Ohio, Kelly Ayotte of New Hampshire and Dean Heller of Nevada — are keeping their positions private for now.

Political strategists and congressional aides who have been lobbying for the bill say they have received private assurances that there will be enough Republican votes to allow the measure to move forward Monday.

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In the House, the best chance for passage this year seems to be to tack the measure onto a larger piece of legislation like the annual National Defense Authorization Act, and hope that conservatives do not revolt.

“If you’ve been told your entire career that Republican primary voters are hostile on these issues, and people have only just started to educate you otherwise, it takes a little while for that to sink in,” said Jeff Cook-McCormac, a Republican lobbyist who has been pushing to get the bill enacted.

While opposition appears less organized compared with previous gay-rights debates in Congress, senators of both parties said the emotion surrounding the issue has certainly complicated efforts to break a Republican filibuster attempt.

One senator recalled having to explain to a colleague that the new law would not, in fact, require insurance companies to pay for sex-change operations.

Another spoke of phone calls from constituents who were convinced that their children could be taught in school by men wearing dresses.

And conservative groups like the Family Research Council are warning their supporters that the bill would force Christian bookstores to hire drag queens.

To break through the misinformation, supporters said, they have presented senators with polls showing that a majority of Republican voters favor protections for gay, lesbian and transgender workers.

And they have made appeals to bedrock Republican principles.

“I’m a Lincoln guy,” said Norm Coleman, the former Republican senator lobbying for the bill, the Employment Nondiscrimination Act. “So if you go back to who we are, what we are about as a party — economic freedom, equality, the right to earn a living — this makes sense.”

It is also smart politics, he added. “Our party has to add, and not subtract, if we’re going to be a successful national party.”

Democrats are confident they will have a good outcome regardless of the final vote, and have pressed ahead despite not being absolutely certain it can pass.

If they succeed, it would be the first time the Senate has passed an anti-discrimination bill that protects gays and lesbians. One failed in 1996, the last time the issue came to a vote on the floor.

And if it fails this time, Democrats will be able to frame the loss as a victory by Republican extremists.

“How can they justify voting against it?” said Barney Frank, the former congressman who tried to get a nondiscrimination bill passed when he was in Congress.

Sen. Susan Collins, R-Maine, who has been leading the effort to persuade more Senate Republicans to vote for the bill, said some colleagues did raise concerns about how the law would have to accommodate people questioning their gender, including one concerned about insurance covering sex changes. But by and large, she said, she came away encouraged that many Republicans seemed to be willing to re-evaluate their views on sexual orientation, gender identity and the law.

“Generally what I’ve found is a real openness to taking a second look at this issue,” she said.

The only Republican senators who co-sponsored the bill are Collins and Sen. Mark Kirk of Illinois. Two others — Orrin Hatch of Utah and Lisa Murkowski of Alaska — voted for the bill in committee. But they are the only four on record in support.

All 55 members of the Democratic majority have said they will vote yes when the bill faces its first filibuster test Monday, meaning at least one more Republican would need to cross the aisle.

Several other votes are expected next week on the bill, including some that could amend it to address Republican concerns about lawsuits and exemptions for religious organizations.

The bill’s main sponsor, Sen. Jeff Merkley, D-Ore., inherited the legislation from Sen. Edward M. Kennedy after Kennedy died in 2009.

Anti-discrimination legislation that applies to sexual orientation has a long and unfulfilled history in Congress dating to 1974 when two House members, Bella Abzug and Edward Koch, first introduced a measure.

Supporters now say they are guardedly optimistic. Despite the broader acceptance of homosexuality and the legislative and legal victories that have propelled the gay-rights movement recently, they say they realize Congress is one domain where they can never be sure of anything.

“It’s nice to have had one year of victories,” said Chad Griffin, president of the Human Rights Campaign. “But we have to remember that was preceded by 30 years of losses.”

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