Black Americans (blacks) have a high prevalence of chronic hepatitis C virus (HCV) infection and respond poorly to therapy with interferon alfa-based regimens, but they have been underrepresented in clinical trials. The aim of this study was to assess the rate of sustained virological response (SVR) to peginterferon alfa-2a (40 kd) in combination with ribavirin in black patients chronically infected with HCV genotype 1. In a prospective, multicenter, open-label trial, 78 black and 28 white American interferon-naïve patients were enrolled to receive once weekly subcutaneous injections of 180 microg peginterferon alfa-2a plus oral ribavirin (1000 mg/d for patients weighing less than 75 kg and 1200 mg/d for patients weighing 75 kg or more) for 48 weeks. Pre- and post-treatment liver biopsies were evaluated for necroinflammation and fibrosis. SVR, defined as undetectable (<50 IU/mL) HCV RNA, was 26% in the black group and 39% in the white group. Although the SVR rate was lower in blacks than in whites, the SVR of 26% represents an improvement over previously reported SVR rates from smaller, retrospective studies of black patients. We also observed improvement in fibrosis in 25% of the black patients. No unexpected adverse events occurred. In conclusion, this prospective study evaluating responses of black patients with chronic hepatitis C to peginterferon alfa-2a/ribavirin has demonstrated that treatment can be safely offered to such individuals with reasonable antiviral and histological benefit.