Staphylococcus saprophyticus is the second most common cause of urinary tract infection (UTI) in young women. Relatively little is known about risk factors for this infection including exposure to vaginal spermicides, which increases the risk of UTI caused by Escherichia coli. We conducted a case-control study in a large health maintenance organization Case patients were sexually active young women with acute UTIs caused by S saprophyticus identified from computerized laboratory files during 1990 to 1993. Population-based control patients were randomly selected from the organization's enrollment files. Exposures such as sexual activity and contraceptive practice were determined by interview. Of 1299 eligible women, 66% (96 case patients and 629 control patients) were interviewed. Case patients were more often unmarried and were more sexually active. Ninety-nine percent of case patients and 57% of control patients reported previous UTIs. Exposure to any type of condom during the previous year was reported by 53% of case patients and 31% of control patients. Exposure to spermicide-coated condoms during the previous month was associated with a higher risk of UTI (odds ratio [OR], 3.8; 95% confidence interval, 1.4-10.3). The OR for exposure during the previous year ranged from 2.2 (95% confidence interval, 1.0-4.8) for less than once weekly to 6.05 (95% confidence interval, 2.2-16.6) for more than twice weekly. In multivariate analyses, younger age (OR, 0.97 per year), intercourse frequency (OR, 1.2 per weekly episode), prior UTI (OR, 3.3), and frequency of exposure to spermicide-coated condoms (OR, 8.4 for more than once weekly and 10.9 for more than twice weekly) were independent predictors of UTI. Among women exposed to spermicide-coated condoms, 74% of UTIs caused by S saprophyticus were attributable to this exposure. Spermicide-coated condoms were associated with an increase risk of UTI caused by S saprophyticus. Because sexual activity and spermicide exposure are important risk factors for UTI caused by both S saprophyticus and E coli, it is likely that they share a similar pathogenesis.