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Domains central to the effects of sexual relationships on the acceptability of a vaginal protection method were explored in 14 focus groups and 38 in-depth interviews with women and men recruited from a health department's sexually transmitted infections (STI) and family planning clinics. Findings indicate that acceptability depended on a couple's relationship type, classified as serious, casual, or “new.” Potential barriers to communication about product use may be overcome through direct or indirect covert use, depending on relationship type. More men than women thought women should always tell their partners if they use microbicides, regardless of relationship type. Results indicate the importance of the relationship context in understanding the likely acceptability of using microbicides, and perhaps any method of STI/HIV protection.