"It's difficult for us to back a candidate our constituents don't believe in and aren't excited about," Tony Perkins, president of the Family Research Council conservative Christian lobbying group, told CNN.
"Some of us just have a hard time supporting a person who said he was going to be more liberal on gay rights than Ted Kennedy," Home School Legal Defense Association Chairman Michael Farris, whose group also advocates conservative political and religious causes beyond home schooling, told the network.
Romney told the Log Cabin Club of Massachusetts in an Oct. 6, 1994, letter, during his unsuccessful U.S. Senate bid to unseat Kennedy, he would "provide more effective leadership" than Kennedy in establishing "full equality for America's gay and lesbian citizens."
Log Cabin Republicans advocate equal rights for all Americans, including lesbian, gay, bisexual and transgender people.
Marjorie Dannenfelser, president of the Susan B. Anthony List, which supports politicians who seek to eliminate legalized abortion, did not mention Romney in a statement praising Santorum's candidacy on his departure.
Santorum did not mention Romney either when he announced in a 12-minute speech Tuesday he and his family decided during the weekend to end his White House campaign.
"While this presidential race for us is over, for me ... we are not done fighting," Santorum said in Gettysburg, Pa.
"This game is a long, long, long way from over," he said.
A Romney statement issued moments after Santorum concluded his remarks called the former Pennsylvania senator "an able and worthy competitor, and I congratulate him on the campaign he ran."
"He has proven himself to be an important voice in our party and in the nation," Romney's statement said. "We both recognize that what is most important is putting the failures of the last three years behind us and setting America back on the path to prosperity."
Santorum did not endorse any candidate but said he would work to defeat President Barack Obama.
Most political observers said Santorum's decision all but cleared the way for Romney, a former Massachusetts governor, to claim the nomination.
But Gingrich, the former House speaker from Georgia, said that was not true, vowing to stay in the race through the Republican National Convention in Tampa, Fla., the week of Aug. 27 "so that the conservative movement has a real choice."
"I humbly ask Sen. Santorum's supporters to visit Newt.org to review my conservative record and join us as we bring these values to Tampa," Gingrich said in a statement. "We know well that only a conservative can protect life, defend the Constitution, restore jobs and growth and return to a balanced budget."
Gingrich later sought to recast the GOP run as a two-man race, telling former Arkansas Gov. Mike Huckabee on his radio show Santorum's exit made "it clearer that there's a conservative, named Newt Gingrich, and there's Mitt Romney."
He said he now relished the "one-on-one" match-up he "spent the whole year hoping to get."
Ron Paul's campaign said the Texas congressman was also still in the race.
It called Paul "the last -- and real -- conservative alternative" to Romney.
Perkins told CNN conservative activists were so unenthusiastic about Romney that many would likely shift their grassroots efforts from the presidential race to congressional contests -- specifically seeking to put the U.S. Senate in Republican hands.
But others said they were prepared to support Romney, now that he has virtually cleared the GOP field.
"Mitt Romney has taken a strong pro-life stance, and so has Rick Santorum, and pro-life people will rally behind whoever the nominee is to defeat Obama," National Right to Life Committee Executive Director David O'Steen told The Washington Post.
Faith and Freedom Coalition Chairman Ralph Reed said Romney "has to build bridges to evangelical voters, who he will need to turn out in large numbers in November."
"I think Romney understands this and will take whatever steps are necessary to energize social conservative voters," Reed told the Post. "Evangelicals will turn out to vote against Obama. Now it's important that they are enthusiastic about voting for the Republican nominee."