Fifty-six consecutive patients with cryptogenic chronic active liver disease were enrolled in a randomized controlled clinical trial of alpha-2a interferon and randomly assigned to a control group (28 patients) and to a treated one (28 patients). All had a histologic diagnosis of chronic active hepatitis (with superimposed cirrhosis in 50% of them) and presented a persistent elevation in aminotransferases, during the last year. Ad-interim analysis shows that 19 out of 28 treated patient (68%) have normalized the aminotransferases during the eight months of therapy, with a statistically significant difference (p less than 0.01) between treated and control group; nevertheless, in 58% of them, we noted rising aminotransferases at low doses of interferon with subsequent normalization when the dose was increased to previous effective levels. Retrospectively, the antibody directed to virus C (anti-HCV) was found positive in 84% of our patients, and its presence was strongly associated with response to interferon treatment. Our preliminary results seem to demonstrate that interferon is truly effective, mainly at high doses, in cryptogenic chronic active liver disease; these data with the high prevalence of anti-HCV and the association between anti-HCV and response to therapy, may confirm a possible etiologic role of virus C in causing this subgroup of liver disease.