Antibody to the hepatitis delta virus (anti-delta) was detected in 112 out of 2487 (5%) individuals fortuitously found to have the hepatitis B surface antigen (HBsAg) in the blood. Liver function was impaired in 38% (43 of 112) of the anti-delta-positive carriers but in only 9% (215 of 2375) of the anti-delta-negative subjects (p less than 0.001). Liver biopsy specimens were obtained from 31 antibody-positive and 97 antibody-negative subjects with impaired liver function. Important histological changes were observed in 61% of the 31 antibody-positive carriers (7 chronic active hepatitis, 4 active cirrhosis, 8 inactive cirrhosis) but in only 19% of the 97 antibody-negative carriers (p less than 0.001). The presence of anti-delta in serum identifies a subpopulation of apparently healthy HBsAg carriers whose risk of underlying liver disease is four times higher than that in the ordinary carrier. The identification of anti-delta in a symptom-free HBsAg carrier with abnormal liver function is thus an indication for a diagnostic liver biopsy.