The safety and efficacy of pegylated interferon (PEG-IFN) alfa-2a and ribavirin were studied among patients treated for genotype 4 chronic hepatitis C. Ninety-five patients with chronic hepatitis C genotype 4 were treated with PEG-IFN alfa-2a (180 microg/week) plus ribavirin (> or =11 mg/kg/day) for 48 weeks. The primary end point was sustained virological response, defined as non-detectable levels of HCV RNA at the end of follow up (week 72). The proportion with sustained virological response was 58/95 = 61.1% (95% CI = 50.5-70.9%). Side effects were generally mild, well managed by dose reductions (in 62% of patients); in only two patients were side effects sufficiently severe to require treatment interruption. Ninety percent of patients adhered to treatment up to week 12, and their sustained virological response rate was higher compared to non-adherent (65% vs. 22%, respectively, P = 0.012). None of the patients who failed to achieve 1 log reduction of viral load by week 8 (n = 15), or 2 log reduction by week 12 (n = 17), had a sustained virological response. In conclusion, sustained virological response in genotype 4 Egyptian patients treated with PEG-IFN alfa-2a and ribavirin was estimated around 60%, intermediate between sustained virological response observed in genotype 1 and genotype 2-3 patients in Western countries. The early virological response (week 4 or week 8) should be investigated as a criterion to decide whether the patient may benefit from a shorter duration of therapy.