Liver biopsies from a total of 240 patients with acute hepatitis A (86 patients), B (78 patients) and non-A, non-B (76 patients) were blindly evaluated for quantitative and qualitative light microscopic differences. No qualitative differences separate the three types of hepatitis, but the frequency and degree of some histological features seem to be characteristic of acute human non-A, non-B hepatitis. The degree of focal necrosis and portal inflammation was less pronounced in the non-A, non-B group as compared to the hepatitis A and B groups (P less than 0.01). Twenty-six percent of the non-A, non-B liver biopsies showed steatosis as compared with 10% and 6% in the hepatitis A and B groups, respectively (P less than 0.01). Bridging necrosis only occurred in liver biopsies from patients with non-A, non-B and B hepatitis. Abnormal bile ducts were detected in a total of five patients, three of whom were found in the non-A, non-B group. A comparison between histological findings in non-A, non-B patients with and without a possible intravenous exposure revealed that steatosis, cholestasis, large piecemeal necrosis and confluent necrosis occurred with the highest incidence in the patients without intravenous exposure, indicating that non-A, non-B hepatitis may be caused by more than one etiological agent.