Elevated neopterin levels in blood or urine have been shown to be a marker for the activation of cell-mediated immunity in vitro and in vivo. To evaluate whether neopterin levels are elevated in patients with acute viral hepatitis, we measured urinary levels in 13 patients with hepatitis A, 26 with hepatitis B, 12 with non-A, non-B hepatitis, 8 with jaundice and/or cholestasis due to biliary and pancreatic disorders and 3 with alcoholic hepatitis and in 62 apparently healthy HBsAg carriers. Neopterin levels in patients with virus-induced hepatitis were significantly higher than those in patients with other diagnoses. Urinary neopterin levels were above normal in 49 of 51 patients with viral hepatitis and elevations during the course of hepatitis showed a pattern similar to that of the usual liver biochemical tests, suggesting that neopterin levels were related to the clinical activity of the viral disease. In patients with non-viral biliary and hepatic disorders, neopterin levels were usually normal and did not correlate with other liver biochemical tests. These findings suggest that cell-mediated immune mechanisms are activated during viral hepatitis and that neopterin measurement may be of value as an additional surrogate marker for non-A, non-B hepatitis.