The prevalence and characteristics of hepatitis C virus (HCV) infection in 226 patients who were seropositive for human immunodeficiency virus (HIV) were determined. Antibody to HCV (anti-HCV) was detected by enzyme immunoassay (EIA), and positive results were confirmed by a neutralization EIA or recombinant immunoblot assay. The prevalence of anti-HCV was 8%. Intravenous drug use was the most common risk factor for HCV infection (61.1% of patients), and 52.4% of intravenous drug users were seropositive for anti-HCV (HCV+). Only 16.7% of HCV+ patients had AIDS, as compared with 37.4% of anti-HCV-seronegative (HCV-) patients (P = .04). The prevalence of hepatitis B virus markers in patients with and without anti-HCV was similar. The CD4+ lymphocyte counts were higher for HCV+ patients than for HCV- patients (P = .001), and the prevalence of anti-HCV decreased in parallel with CD4+ counts. Elevated liver function test values were more common for HCV+ patients than for HCV- patients (61.1% vs. 26.0%; P < .01), but abnormalities were usually slight (< 2-fold elevation in values). HCV viremia was detected by the polymerase chain reaction in 88.2% of HCV+ patients. Despite the coexistence of HIV and HCV infection, liver disease appeared to be mild, and HCV infection did not appear to increase the severity of HIV infection. Serological tests for HCV appear to underestimate the prevalence of HCV infection in patients with advanced HIV infection or AIDS.