The seroprevalence and risk factors for hepatitis B virus (HBV) infection were determined among 1,497 heterosexuals with no history of intravenous drug use (median age 32, range 15-78) treated at a sexually transmitted disease clinic in Rome. A total of 329 (22.0%) had antibodies to HBV core antigen (anti-HBc), a rate nearly four times as high as the 5.8% found recently in a national sample of young male adults, ages 18-26 years. Multiple logistic regression analysis showed that the risk of anti-HBc positivity was independently associated with male sex, increasing age, lower level of education, three or more sexual partners in the previous year, and positive syphilis serology. Lack of condom use, history of nonulcerative sexually transmitted diseases, and genital herpes were not associated with anti-HBc positivity. These findings confirm that heterosexual exposure plays an important role in the spread of HBV infection. Furthermore, these data indicate that individuals with more than two sexual partners a year and those with positive syphilis serology should be immunised against HBV.