During a 33-month period, 295 patients with acute viral hepatitis were admitted to a state hospital for civil servants and their dependents in São Paulo, Brazil. Seventy-nine per cent (232) were HBsAg negative. To define the contribution of non-A, non-B viral hepatitis to hepatitis morbidity in this population, further serological studies were performed in 147 confirmed HBsAg-negative patients. One hundred and twelve (76%) were serologically classified as hepatitis A based on identification of IgM antibody to hepatitis A virus. Thirty patients (20%) without IgM antibody to hepatitis A virus, HBsAg, or anti-HBc were categorized as the non-A, non-B hepatitis group. The remaining five patients had probable hepatitis B (IgM antibody to hepatitis A virus negative, HBsAg negative, anti-HBs negative but anti-HBc positive). These data suggest that all three etiological forms of viral hepatitis are endemic in São Paulo. Epidemiological, clinical, and laboratory features were compared to the hepatitis A and non-A, non-B hepatitis groups. Patients with non-A, non-B hepatitis were significantly older than patients with hepatitis A (mean age +/- S.D.: 30 +/- 22 years vs. 9 +/- 9 years, p less than 0.001). Contact with hepatitis or jaundice was recognized in 26 (23%) of 112 hepatitis A patients and 3 (10%) of 30 non-A, non-B patients, a difference which was not statistically significant. Parenteral exposures were identified in 13 (43%) of 30 patients with non-A, non-B hepatitis and 23 (21%) of the 112 hepatitis A patients. Blood transfusion in the 2 months preceding onset of illness was reported in 5 (17%) of the 30 non-A, non-B patients and in none of the hepatitis A group (p less than 0.001). Although prodromal symptoms and fever were more common in patients with hepatitis A, neither these nor other clinical features appeared to be distinguishing characteristics. Similarly, mean peak SGPT levels, peak SGPT levels of greater than or equal to 1,000 IU/per liter, and the mean duration of SGPT elevations for each group were not significantly different. Mean peak serum bilirubin levels were slightly higher in the non-A, non-B group than in the hepatitis A group (7.6 +/- 8.0 mg per dl vs. 5.1 +/- 2.7, p less than 0.01) and peak bilirubin levels greater than or equal to 10 mg per dl were found in 27% of the non-A, non-B group and 5% of the hepatitis A group (p less than 0.001). Whether the higher bilirubin levels reflect an agent-related phenomenon or an older population of affected patients is uncertain.