BACKGROUND AND OBJECTIVES: Potential rectal microbicides, as an adjunct to condoms for HIV/STD prevention, have not been studied previously. GOAL OF THIS STUDY: Advantage 24 (1.5 ml of a bioadhesive gel containing 52.5 mg nonoxynol-9 administered by single-use applicator)-under investigation as a vaginal microbicide-was evaluated for acceptability among male couples. STUDY DESIGN: Twenty-five HIV-negative and 10 HIV-positive male couples participated in a frequency use escalation trial. Diaries and self-administered questionnaires assessed product use, acceptability, sexual behavior, and gastrointestinal and urologic side effects. RESULTS: Excluding participants who felt no need for an HIV prevention method, 58% said they would use Advantage 24 if approved for rectal use; 69% of receptive users reported rectal fullness and related side effects after insertion of the gel, and 68% reported applicator-related discomfort; 59% of insertive participants found the gel too sticky. CONCLUSIONS: Acceptability remains inconclusive and warrants further study of redesigned applicators and ways to minimize rectal side effects.