The purpose of this prospective work was to study a possible relationship between autoantibodies, cryoglobulinaemia and liver histologic lesions in chronic hepatitis C. Ninety three patients (mean age: 43.3 years) with histologically proven chronic hepatitis were studied. Chronic hepatitis was associated with cirrhosis in 18 cases. Auto-antibodies detection was performed in the serum of all patients and cryoglobulinaemia detection was performed in 47 patients. The prevalence of auto-antibodies was also studied in 45 blood donors (control group) and 30 patients with chronic hepatitis B. Histologic study included Knodell score and semi-quantitatively expressed histologic lesions considered as more specific of chronic hepatitis C. Twenty six of the 93 patients (28%) had at least an autoantibody with a level > or = 1/100. The autoantibodies prevalence was: smooth muscle: 15%, antinuclear: 15%, LKM 1: 1.2%, mitochondrial: 0. A mixed cryoglobulinaemia was present in 23 of 47 patients (49%). The prevalence of anti-smooth-muscle autoantibodies was significantly increased in hepatitis C patients compared with the control group (P < 0.05). The histologic Knodell score was 7.3 +/- 3.6. The histologic lesion prevalence was: portal tract lymphoid follicles: 97%, acidophil bodies: 85%, intra-sinusoidal lymphoid infiltrates: 71%, steatosis: 61%, microgranulomas: 54%, biliary duct tract damages: 53%. No statistical significant correlation was found between autoantibodies prevalence and liver histologic lesions. The Knodell score was only significantly increased in patients with mixed cryoglobulinaemia (8.4 +/- 3.6 vs 6.2 +/- 2.8) (P < 0.05). These results suggest that the autoantibodies presence in chronic hepatitis C does not change hepatic histologic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)