The immunological effects of interferon (IFN)-alpha administration were evaluated in 15 patients with cHCV infection. Individuals were treated with 6 MU of lymphoblastoid IFN-alpha three times a week for 6 months and with 3 MU three times a week for an additional 6 months. Patients were divided into responders (12 subjects) and nonresponders (3 subjects), respectively, according to alanine aminotransferase serum levels at the end of treatment. Before therapy (T0), absolute numbers of CD3+, CD4+, CD8+, CD14+ and CD16+ cells were significantly reduced in both groups when compared to normal values. At the same time, all patients displayed a profound decrease of phagocytosis and killing exerted by both polymorphonuclear cells (PMN) and monocytes (MO). However, MO Killing resulted to be normal in the responder group. With special reference to T cell function, T cell mediated antibacterial activity, using Salmonella typhi as a target, was also significantly reduced. After therapy (T12), in responder patients a significant increase of CD3+, CD4+, CD14+ and CD16+ cell absolute numbers was observed, while phagocytic and T cell functions were still depressed. Among the nonresponders, in two of three patients IFN-alpha administration gave rise to an increase (above normality) of CD3+, CD4+, CD8+, CD14+, CD16+ and CD20+ cell absolute numbers, while in one patient the same markers dramatically dropped below normal range. In two patients, antibacterial activity was significantly augmented by IFN-alpha treatment, whereas in one patient no modification was observed. Finally, in the same patients IFN-alpha did not correct PMN and MO pretreatment deficits.