An epidemiologic study of penile cancer involving 141 cases and 150 community controls was undertaken in a high-risk area in China. Personal interviews, as well as physical examinations among the prospectively ascertained subjects, enabled evaluation of a variety of potential risk factors. Strongly related to risk were conditions restricting the motility of the foreskin, including phimosis or paraphimosis, particularly when so severe that circumcision was used for treatment. Poor hygiene practices also appeared to increase risk, particularly as evidenced by detection of smegma on physical examination, although it was difficult to decipher whether this association was etiologic or merely a consequence of disease. A sexual relationship outside of marriage was associated with a RR of 1.7, and appeared to be a more important discriminator than number of lifetime sexual partners. Risk was increased among subjects reporting previous genital conditions, particularly sexually transmitted diseases, and physical examinations revealed the appearance of genital warts among 13 cases vs. I control. Interviews with wives of study subjects failed to provide evidence of a "female factor" in the etiology of penile cancer. This study supports the need for further evaluation of the role of hygiene and sexually transmitted agents in the etiology of penile cancer.