In order to evaluate the response to ribavirin in previously untreated patients with chronic hepatitic C, 39 patients were selected for a double-blind prospective and randomized trial, and divided into two groups: ribavirin-group (19 patients) and placebo-group (20 patients). Ribavirin was administered orally for 24 weeks (600 mg/day, followed by 1,000 mg/day and 1,200 mg/day each one for 8 weeks). After 3 months of drug administration, the patients were evaluated by measuring biochemical, virologic and histologic responses. After this phase, ribavirin was offered to the patients who had received placebo (second phase). The results showed that the patients who received ribavirin showed a higher reduction in serum alanine aminotransferase (ALT) activity than patients in the placebo group. Among the patients in the ribavirin-group, a complete biochemical response (ALT levels normalized) was observed in 3 patients (16%), and a partial response (reduction greater than 50% of the initial value of ALT activity) in 4 (21%). In the 20 patients in the placebo group, only 1 showed a partial response (5%). In the second phase of the study, among 16 patients who received ribavirin, 4 (25%) showed a complete and 5 (31%) a partial biochemical response. HCV-RNA did not become negative in any patient during the two phases. A reduction in the score of portal and lobular activity was observed in patients who received ribavirin, but statistical analysis did not identify differences. This study showed that ribavirin alone induces a biochemical response (ALT reduction) in some patients with chronic hepatitis C, which may be associated with a reduction in hepatic inflammatory activity reduction, but the changes are not sufficient to recommend initial monotherapy with ribavirin.