The prevalence of hepatitis C virus antibody and its relationship to the severity of liver disease in chronic alcoholic patients has been assessed, using a recently developed enzyme immunoassay and confirmed by a recombinant immunoblot assay, in 144 patients (mean age +/- S.D. = 44.4 +/- 11.3 yr) who had consumed greater than 80 gm/day ethanol for greater than 5 yr. Hepatic disease was evaluated by clinical and biochemical studies and by liver biopsy when appropriate. In addition, 76 liver biopsy specimens from these patients were analyzed to determine whether liver lesions were similar in alcoholic patients with and without hepatitis C virus antibodies. According to clinical and histological features alcoholic patients were divided into five groups: normal liver (45 patients), fibrosteatosis (20 patients), alcoholic hepatitis (14 patients), cirrhosis (61 patients) and chronic hepatitis (4 patients). Hepatitis C virus antibodies were present in 35 alcoholic patients (24.3%). The prevalence of hepatitis C virus antibodies correlated with the severity of liver injury: 2.2% in patients without liver disease, 20% in those with fibrosteatosis, 41.4% in those with alcoholic hepatitis and 42.6% in those with cirrhosis. Hepatitis C virus antibodies were found in one of the four patients with chronic hepatitis (p less than 0.001). Furthermore, patients positive for hepatitis C virus antibodies with normal liver or fibrosteatosis showed higher serum bilirubin and gamma-globulin concentrations and lower aminopyrine breath test scores than did patients negative for hepatitis C virus antibodies with normal liver or fibrosteatosis. Similar differences between patients with and without hepatitis C virus antibodies were observed in patients with alcoholic hepatitis or cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)