HCV infections are two-times more prevalent in black Americans than in whites. We previously reported that treatment with peginterferon alfa-2a plus ribavirin produced a sustained virologic response (SVR) rate of 26% in blacks, a lower efficacy compared with the SVR in whites. Here we detail the safety profile of peginterferon alfa-2a plus ribavirin and the relationship between treatment adherence, defined by cumulative drug exposure, and SVR in 78 black patients infected with HCV genotype 1. Sixty-two (79%) patients completed 48 weeks of combination treatment. Peginterferon alfa-2a dose was modified for neutropenia in 36 patients (46%), whereas ribavirin dose was modified due to anemia in 31 patients (40%). The SVR rate was related to medication exposure, based on the percentage of the planned doses of peginterferon and ribavirin that the patients received. The SVR rates were 33, 25 and 0% in patients who received >80, 61-80 and <or=60% of the planned peginterferon, respectively. The SVR rates were 28, 33 and 18% in patients who received >80, 61-80 and <or=60% of the planned ribavirin. The SVR rate was 29% (11 of 38) in patients who received >80% of the total planned doses of both peginterferon and ribavirin and 7% (1 of 14) in patients who received <or=80% of both medicines. The SVR was 30% in patients who received >60% exposure to both, and 0% in patients with <or=60% exposure. In conclusion, peginterferon alfa-2a plus ribavirin demonstrated good safety and tolerability profiles in blacks infected with HCV genotype 1. Adherence to at least >60% of the planned peginterferon alfa-2a and ribavirin doses for 48 weeks was associated with a greater SVR in black patients with HCV genotype 1 infections.