The effectiveness of a daily continuous infusion of interferon-alpha was evaluated in 12 patients (10 males, 2 females; mean age of 33 years, range 19-62) with biopsy-proven chronic active hepatitis C. Nine million units (MU) of recombinant interferon-alpha 2A (rIFN-alpha 2A) were administered by continuous subcutaneous infusion with a portable syringe pump, Graseby model MS 16A, for 24 h over 28 days. A significant decrease (P less than 0.01) in median serum alanine aminotransferase (ALT) levels was observed after the first week of treatment (96 IU/L, range 58-263) with respect to the pre-treatment values (188 IU/L, range 119-670). ALT became normal in four patients only by the fourth week. When IFN was interrupted, an increase in ALT was observed in all patients (1.5 to 5 times the pre-treatment values). The maximum decrease in ALT coincided with a significant increase in serum levels of the enzyme 2',5'-oligoadenylate (2-5A) synthetase (two to fourteen times the pretreatment values) and these parameters were inverse-correlated (r = -0.598, P less than 0.05). 2-5A synthetase levels returned to pre-treatment values after discontinuing IFN administration. Hepatitis C virus (HCV) RNA (as detected by the polymerase chain reaction using oligonucleotide primers of the NS5 region) was positive in all cases, remaining so during the treatment period. IgM antibody to HCV (as tested by ELISA) was present in 10/12 cases at baseline without changes throughout the study. No irreversible side effects were noted during therapy, which needed to modify the schedule.(ABSTRACT TRUNCATED AT 250 WORDS)