The relationship between selected urinary tract and genital diseases and the risk of bladder cancer was analyzed using data from a case-control study of 364 cases of bladder cancer and 447 controls hospitalized for acute, nonneoplastic, nongenital tract conditions, unrelated to known or suspected risk factors for bladder cancer. Cystitis was reported by 20% of the cases and 8% of the controls, corresponding to a multivariate relative risk (RR) of 3.8 (95% confidence interval, 2.4 to 5.9). No association was observed with urinary tract stones (RR = 1.2). With reference to genital diseases, the RR was elevated for gonorrhea (RR = 2.8, 95% confidence interval, 1.0 to 4.5) and condylomata acuminata (RR = 5.9, 95% confidence interval 1.0 to 3.6) but not for syphilis. The risk increased with the number of episodes of cystitis (RR = 5.0 for greater than or equal to 4 episodes, chi 2 for trend = 33.04, P less than 0.001), was higher during the last 15 years after the first episode (RR = 5.1 versus 2.3 for over 15 years), and was not heterogeneous across strata of age and sex. The interaction between urinary tract infections and tobacco appeared multiplicative, with RR = 2.4 for ever smoking, 3.2 for cystitis alone, and 10.3 for both exposures. The present study, besides providing further quantitative evidence of a relationship between urinary tract infections (and, possibly, some genital infections, too) and bladder cancer, indicates that the role of infections is probably in one of the latter (promoting) stages of the process of carcinogenesis and suggests a multiplicative interaction with smoking. In terms of prevention and public health, therefore, it is thus important to avoid at least one exposure for subjects with a history of urinary tract infections who smoke tobacco.