The dosage and duration of Chronic Hepatitis (CH) C therapy with alpha (alpha-IFN) is still an unresolved problem. Considering mainly antiviral activity of alpha-IFN, the authors carried out research on 35 patients with CH-C to evaluate the efficacy and safety of long term therapy and to compare recombinant alpha-IFN-2a with recombinant alpha-IFN-2b. 21 patients (Group A: 20 males, 1 female, mean age 48.8 years, 14.2% CPH, 76% CAH, 9.5% AC) were treated with r-alpha-IFN-2a; 14 patients (Group B: 7 males, 7 females, mean age 45.2 years, 7.1% CPH, 78.5% CAH, 14.3% AC) were treated with r-alpha-IFN-2b, at a dosage of 3 MU thrice weekly (TIW) for 12 months; the follow-up was from 6 to over 24 months. Complete Response (CR) was achieved in 49.3% of the patients treated, Long Term Response (LTCR) in 19.3%, Partial Response (PR) in 29% and No Response (NR) in 22.6%), Delayed CR in 6.5%. The authors found a similar number of CR and LTRC in group A and group B; a greater percentage of PR in group A and a greater percentage of NR in group B. Early and serious side effects in 4 patients, late and serious side effects in 2 patients were observed. The date suggest that the long term therapy of CH with r-alpha IFN is effective in inducing clinical and biochemical remission in a large portion of patients and a greater number of sustained response, with respect to a therapy schedule of 6 months even at greater dosages.