The aim of this study was to assess the efficacy and tolerance of interferon alpha (IFN alpha) treatment of chronic hepatitis C in HIV-seropositive patients. Seventeen patients with actively replicating hepatitis C were consecutively enrolled and treated with IFN alpha 5 MIU three times a week and followed up for at least 6 months after cessation of treatment. Eight patients responded to IFN alpha therapy with a complete remission of signs of active hepatitis and viral replication (ALT, HCV-RNA) at the end of treatment with IFN alpha. A sustained complete remission (ALT, HCV-RNA) for at least 6 months after the end of treatment was achieved in five of these eight patients. Complete responders had higher CD4+ cell counts (median 525/microliter) compared to non-responders (median 245/microliter) (p < 0.001). All patients but one completed at least 4 months of treatment. No severe toxicity (> WHO grade 2) due to IFN alpha treatment occurred. The results indicate that IFN alpha treatment of chronic hepatitis C in HIV-seropositive patients is successful in a considerable number of cases. Success of treatment with IFN alpha is related to higher CD4+ cell counts.