Hepatic steatosis is common in chronic hepatitis C and has been linked to concurrent obesity, insulin resistance, diabetes, disease severity, and poor response to therapy. Racial differences in rates of obesity and diabetes may contribute to racial differences in hepatic steatosis and treatment response. The aim of the present study was to compare hepatic steatosis and its associations between African American (AA) and Caucasian American (CA) patients with chronic hepatitis C, genotype 1, participating in a prospective study of peginterferon and ribavirin therapy. Liver biopsy results were available from 194 AA patients and 205 CA patients. The 2 groups were compared for anthropometric, clinical, and biochemical features and insulin resistance estimated by the homeostasis model assessment index (HOMA-IR). Sixty-one percent of the AA patients and 65% of the CA patients had hepatic steatosis (P = 0.38). In univariable analysis, steatosis was associated with HOMA-IR, body mass index, waist circumference, serum triglycerides, aminotransferase level, and histological scores for inflammation and fibrosis. After adjusting for these features, AA patients had a lower risk of steatosis than did CA patients (OR 0.54, 95% CI 0.32-0.91, P = 0.02). Insulin resistance but not steatosis was associated with a lower rate of sustained virological response when adjusted for known factors that predict response (relative risk 0.87, 95% CI 0.77-0.99, P = 0.028).