Serum samples from 735 homosexual or bisexual men were tested for antibodies to hepatitis C virus (HCV) and serologic markers of hepatitis B virus (HBV), and risk factors for each infection were compared. Thirty-four (4.6%) were confirmed HCV-positive compared with 81% positive for one or more HBV serologic marker(s). History of intravenous drug use (IVDU) and blood transfusion were significantly associated with HCV positivity (odds ratio [OR] = 14.3 and 4.4, respectively), but neither was significantly associated with HBV positivity. Sexual behavior was significantly associated with infection with both viruses. When IVDU and blood transfusion were controlled for, HCV infection was marginally associated with > 50 sex partners/year (OR = 2.1), > 25 oral receptive partners (OR = 2.4), and > 25 anal receptive partners (OR = 1.9). HBV infection was more strongly associated with the same variables. HCV infection is uncommon in homosexual men and IVDU is the primary route of transmission, but sexual transmission also occurs, albeit infrequently.