To determine whether specific sexually transmitted diseases were associated with an increased risk of vulvar cancer, we conducted a case-control study among residents of three countries in western Washington. We identified, interviewed, and obtained blood samples from women with in situ (n = 180) and invasive (n = 53) vulvar cancer, 18-79 years of age, who were first diagnosed with these diseases during 1980-1988. We compared their responses with those of 466 women from the general population who were identified by means of random digit dialing. On average, women with vulvar cancer reported a greater number of prior sexual partners than did controls. The risk of vulvar cancer was elevated among women who reported a prior history of condyloma (for in situ cancer, RR = 15.8; for invasive disease, RR = 17.3) or gonorrhea (for in situ cancer, RR = 2.2; for invasive disease, RR = 5.0). Women who were seropositive to herpes simplex virus type 2 (HSV-2) were at higher risk for carcinoma in situ than were controls (RR = 2.0). A history of nonspecific vaginitis, trichomoniasis, syphilis, or seropositivity to cytomegalovirus was not related to case-control status. These results indicate that only a subset of sexually transmitted diseases, particularly human papillomavirus, may play a role in the development of vulvar cancers.