Studies have suggested that African American patients infected with hepatitis C virus (HCV) do not respond as well to treatment with interferon (IFN) as white patients. Here we analyzed the difference in the viral kinetic response between genotype 1 HCV-infected African American patients (n = 19) and white patients (n = 16). Patients were treated with 10 mIU IFN-alpha2b daily with or without ribavirin for 1 month followed by 3 mIU IFN-alpha2b 3 times a week with ribavirin. The kinetic parameters (epsilon, treatment effectiveness at inhibiting virion production; delta, loss rate of virus-producing cells; c, clearance rate of free virions; tau, delay until viral decline starts) were estimated from the viral load decay profiles using a previously described mathematical model. Differences in early kinetic parameters and viral negativity frequencies at weeks 4, 12, and 48 were compared. Ribavirin did not appear to enhance any of the viral kinetic parameters, although this may have been due to the high dose of IFN used. African American patients exhibited significantly (P =.005) lower drug effectiveness (88.6% vs. 98.2%) compared with white patients, accounting for a 0.8 log lower HCV RNA decrease in the first 24 hours of treatment. Significant differences (P =.006) were also noted for delta. There was no correlation between any of the viral kinetic parameters and either age, body mass index (BMI), or genotype 1 subtype. No patient achieved viral negativity at weeks 4, 12, or 48 without an epsilon greater than 90%. The mean viral decline and viral negativity rates were statistically different between the two races; however, when controlling for treatment effectiveness, these differences were no longer apparent. In conclusion, the failure of IFN response in African American patients infected with genotype 1 HCV is in part due to an impaired ability to inhibit viral production.