Background: The purpose of this study was to compare the efficacy of 0.75% metronidazole vaginal gel with no treatment in patients who have had a minimally abnormal Papanicolaou smear. Methods: One hundred forty-five patients whose initial Papanicolaou smears were limited by inflammation or benign cellular changes, reactive cellular changes, or atypical squamous cells of undetermined significance that did not favor a neoplastic process were randomized to 5 days of treatment with 0.75% metronidazole vaginal gel or to a control group receiving no treatment. Papanicolaou smears were repeated after 3 to 4 months. Results: Cytologie findings of the follow-up Papanicolaou smears were normal in 61 of 114 (54%) of patients. Sixty-two percent (n = 37) of the Papanicolaou smears in the control group converted to normal on follow-up, whereas 44% (n = 24) of the Papanicolaou smears in the treatment group converted to normal (P = .07). Only one follow-up Papanicolaou smear worsened to low-grade squamous intraepithelial lesion. In no subgroup was treatment effective. Conclusions: Empiric treatment for an asymptomatic, minimally abnormal Papanicolaou smear with 0.75% metronidazole vaginal gel before a repeated cytologie examination did not improve the rate of reversion to normal cytologic findings.