Since metronidazole is a mutagen in vitro, there is concern about the widespread systemic use of this drug in women with trichomoniasis, particularly those who are pregnant. A randomized, double-blind, placebo-controlled trial compared a single 2-g intravaginal dose of metronidazole cream with a single 2-g oral dose of metronidazole in patients with a culture positive for Trichomonas organisms. Of the 302 preenrollment cultures completed, 94 (31%) were positive. Sixty-one patients were enrolled in the study. Each received either oral placebo and intravaginal metronidazole or intravaginal placebo and oral metronidazole. Follow-up cultures were done on posttreatment day 3-5. Of the 53 evaluatable patients, 14 (50%) of 28 in the intravaginal group and 22 (88%) of 25 in the oral group were microbiologically cured (P = .0037). Single-dose intravaginal metronidazole is inferior to single-dose oral metronidazole and cannot be relied on as an alternative therapy.