The likelihood of a sustained response to a course of interferon in patients with chronic hepatitis C correlates with several clinical and viral factors, including age, viral genotype and initial levels of hepatitis C virus (HCV) RNA in serum. The role of race and ethnicity has not been assessed. We evaluated the association of race with response to interferon in a large randomized, controlled trial using either consensus interferon (9 g) or interferon alfa-2b (3 million units) given three times weekly for 24 weeks. African-American patients participating in the study were similar to white patients in mean age (43 vs. 42 years) and baseline levels of HCV RNA (3.6 vs. 3.0 million copies/mL) but had lower rates of cirrhosis (5% vs. 12%) and more frequently had viral genotype 1 (88% vs. 66%: P β«Ψβ¬ .004). Most strikingly, the rates of end-of-treatment and sustained virological responses were lower among the 40 African-American patients (5% and 2%) than among the 380 white patients (33% and 12%) (P β«Ψβ¬ .04 and .07). Rates of response among Hispanic and Asian-American patients were not statistically different than non-Hispanic white patients. Median viral levels decreased by week 24 of therapy by 2.5 logs in white patients (from 3.0 to 0.012 million copies/mL) but by only 0.5 logs among African-American patients (from 3.6 to 1.8 million copies/mL). Thus, there are marked racial differences in virological responses to interferon in hepatitis C that must be considered in assessing trials of interferon therapy and in counseling patients regarding treatment. The differences in response rates are as yet unexplained. (HEPATOLOGY 1999;30: 787-793.) Chronic hepatitis C is the major cause of chronic hepatitis in the United States, Europe, and Japan, ranking equal to alcohol-induced liver disease as a cause of cirrhosis, endstage liver disease, and hepatocellular carcinoma. 1 Populationbased surveys indicate that 1.5% to 2.0% of the general Abbreviations: HCV, hepatitis C virus; PCR, polymerase chain reaction.