During a survey of acute symptomatic viral hepatitis conducted in Padua over the last 16 years, 404 (20%) cases of non-A, non-B hepatitis were observed, including 55% with overt parenteral exposure (35% drug abusers) and 45% with unknown exposure. Between 1978 and 1982 the attack rate of the disease increased significantly (p < 0.01) in males, (from 3.8 to 17.3/10(5) inhabitants), in adolescents and in youths. The prevalence of drug abusers rose up to 58% in 1982 suggesting the occurrence of an outbreak in this risk group. In subsequent years the attack rate returned to initial levels in males, although drug abuse still remains the single most important route of infection, and declined in females, especially after the disappearance of post-transfusion hepatitis since 1991. Retrospective anti-HCV testing of patients seen up to 1990 and prospective investigation of patients hospitalized later have shown an antibody prevalence of 88% among parenterally transmitted cases, and of 29% in the other patients, without significant differences between the prospective and the retrospective study. These findings suggest that an outbreak of hepatitis C occurred in our area in the early eighties and that drug abuse is still the most important mode of transmission of acute hepatitis C.