The association of cirrhosis with pigment gallstones has been noted in numerous autopsy studies. However a direct relationship between alcoholism and pigment cholelithiasis has not been previously demonstrated. We have classified 123 cholecystectomy patients according to stone type and correlated the resulting categories with hepatic morphology, drinking history, and hematological data. Pigment stones were found in 79% of biopsy-verified cirrhotic patients but in only 26% of noncirrhotics. In patients without cirrhosis a positive history of alcoholism was found associated with pigment gallstones more often than with cholesterol or mixed stones (36% vs. 10%). Similarly, the mean red cell volume (MCV), a sensitive marker of alcoholism, was significantly increased in patients with pigment stones (93.6 mu 3 vs. 89.6 mu 3). We conclude that both cirrhosis and alcoholism predispose to pigment gallstone formation and that the effect of alcoholism may occur independent of cirrhosis. This suggests that the apparent association of cirrhosis with pigment stones may, in fact, result from a direct effect of long-term ethanol ingestion on red blood cells, liver, or bile.