Limited information is available on the prevalence of gallstones in the first-degree relatives of gallstone patients. Three groups of subjects were studied by real-time ultrasound examination: group A, 105 index gallstone patients (male/female; 20:85); group B, 330 first-degree relatives of index patients; group C, matched controls for group A (n = 105) and group B (n = 330) subjects. Dietary, anthropometric, and biochemical investigations were carried out. In 39 of 105 (37%) index cases, one or more additional family members had gallstones (positive-index case). The positive-index cases were younger than the remaining index cases (mean age, 33.1 +/- 14 vs. 44.5 +/- 13.1 years; P < .05). Fifty-one of 330 (15.5%) first-degree relatives had gallstones, nearly four and a half times (95% confidence interval [CI], 2.4 to 8.5) more often than in the matched control population (12 of 330 [3.6%]). Thirty-three of 51 (65%) positive relatives were women; mother (37.3%), sister (17.6%) or daughters (10%) to the index patients. There was no difference in the diet, physical activity, and serum lipid profile between the positive index patients and the remaining gallstone patients and positive relatives and their controls. Our results show that there is a strong familial predisposition for gallstone formation. Female relatives of young gallstone patients should be routinely screened for gallstones.