Background: African Americans with genotype 1 chronic hepatitis C attain a sustained virologic response (SVR) at only approximately one-half the rate of whites after peginterferon and ribavirin treatment. The serum concentration of 25-hydroxyvitamin D [25(OH)D] has recently been established as a predictor of treatment response. Therefore, the low serum concentrations of 25(OH)D found among African Americans may contribute to the low response rate; however, to our knowledge, none of the studies of vitamin D in chronic hepatitis C treatment have included a significant number of black patients. Objective: The objective was to compare the relation between the 25(OH)D concentration and genotype 1 chronic hepatitis C treatment response in African Americans with that in whites. Design: This cross-sectional analysis included 106 African American and 65 white patients with genotype 1 chronic hepatitis C. Results: Consistent with previous studies, we found that the SVR rate in the white patients increased significantly with an increasing serum concentration of 25(OH)D [SVR rates were 20%, 46%, and 70% for 25(OH)D serum concentrations <20, 20-35, and >35 ng/ mL, respectively; P-trend = 0.008]; however, there was no relation between the SVR rate and 25(OH)D serum concentration in the African American patients [SVR rates were 32%, 28%, and 33% for 25(OH)D serum concentrations <20, 20-35, and >35 ng/mL, respectively; P-trend = 0.832]. We also found an analogous racial difference in the relation between the extent of liver fibrosis and the 25(OH)D concentration. Conclusion: Racial differences in vitamin D physiology or race-specific factors that modify the effects of vitamin D may affect the immune response to genotype 1 hepatitis C virus.