Genital irritation and user acceptability was compared after seven nightly bedtime exposures to 1.2% C31G hydroxyethyl cellulose (HEC), 2% nonoxynol-9 (N-9) (Gynol II) or HEC vehicle alone. Sixty healthy women over 18 years old at low risk for sexually transmitted disease with normal menses were randomly assigned to one of three groups. Entrance and exit pelvic exams documented vaginal pH and Gram stain. Genital irritation was assessed by patient diaries, a telephone call 24 to 48 h after first use, colposcopy done the day after last product use, and an acceptability questionnaire at exit. Eighty percent of the women using C31G HEC experienced symptoms of vaginal burning or heat compared to 25% of the N-9 users and 5% of the vehicle users. Colposcopic findings were similar for the active treatments of C31G HEC and N-9: 50% vs. 60% developed new lesions, 25% vs. 20% had lesions that disrupted epithelial integrity, and 50% vs. 45% had minor lesions, respectively. Findings with the HEC vehicle were half as frequent. Twelve percent of women had epithelial disruption that was assessed by the colposcopist as applicator-related. Gram stains were half as likely to show bacterial vaginosis after N-9 use (6 --> 3) and one fourth as likely after vehicle or C31G HEC use (4 --> 1). When asked if they would use the product if it were an effective contraceptive, 55% of the vehicle users, 35% of the N-9 users, and 25% of the C31G HEC users agreed. Product acceptability of C31G HEC was limited by the sensation of heat or burning. The C31G HEC product had a similar safety profile to N-9 in this comparative trial.