A randomized, clinical trial was conducted to evaluate the spermicidal agent nonoxynol 9 as prophylaxis for sexually transmitted diseases. Eight hundred eighteen women using birth control who attended a sexually transmitted disease clinic were evaluated monthly for trichomoniasis, candidiasis, and bacterial vaginosis for 6 months. Women using the active spermicide experienced a somewhat lower incidence rate of trichomoniasis (relative rate 0.83; 95% confidence interval 0.61 to 1.12) and bacterial vaginosis (relative rate 0.86; 95% confidence interval 0.69 to 1.12) as compared with placebo users. The rate of candidiasis was nearly identical for spermicide and placebo users (relative rate 1.02; 95% confidence interval 0.77 to 1.35). The number of sexual partners during the preceding month was related directly to the occurrence of trichomoniasis (p = 0.047) and bacterial vaginosis (p = 0.009) but not candidiasis (p = 0.99). Subjects using oral contraceptives experienced a statistically significant lower rate of trichomoniasis than did women using an intrauterine contraceptive device or who had had a tubal ligation (relative rate 0.56; 95% confidence interval 0.39 to 0.81).