Abstract In a study of patients with thalassemia major by oral cholecystography, the incidence of cholelithiasis is determined. Six of 26 patients aged ten years and older have biliary calculi; in addition, gallstones have been demonstrated during life or at autopsy in 7 of 35 who have died. The association of gallstones with thalassemia, less frequent than in hereditary spherocytosis, has the same degree of magnitude as the relationship in sickle-cell anemia. The authors formulate an explanation for these different frequencies of stone formation in hemolytic disease.