Clinical resolution of acute hepatitis C occurs in a limited proportion of cases. However, the rate of hepatitis C virus persistence remains unclear. For this purpose, we conducted a serial study of 60 patients with hepatitis C virus infection from the early stage of the disease for 24 to 80 months (average 50 months). Fourteen cases who recovered from acute hepatitis were selected from this group for prospective analysis of the behavior of liver enzymes, anti-HCV antibodies (RIBA II, Ortho Diagnostic System) and hepatitis C virus-RNA in serum and in peripheral blood lympho-mononuclear cells by nested polymerase chain reaction. Primers were derived from the 5'-untranslated region of the hepatitis C virus genome and the amplified products were detected by gel electrophoresis and a DNA enzyme immunoassay. All patients except two showed early recovery from acute hepatitis that occurred within 3 months from clinical onset. Transaminase normalization was always preceded by clearance of serum hepatitis C virus-RNA, which remained negative throughout follow-up. During the resolution phase of the disease a progressive decline in the antibody response was observed in most of the patients. At the end of the study anti-C100 was negative in half the cases, while anti-C33 and anti-C22 became negative or borderline in five cases. Hepatitis C virus-RNA was found in the peripheral blood lympho-mononuclear cells, but not in the serum, of only one of eight patients tested.(ABSTRACT TRUNCATED AT 250 WORDS)