Despite the very high prevalence of gallstone disease, studies of familial factors are very few, and asymptomatic family members were not studied. We studied, in a prospective manner, the frequency of gallstones in 171 first-degree relatives of patients with proven gallstones compared with 200 matched controls. All subjects were studied by oral cholecystography, and their height, weight, blood glucose, cholesterol, and other parameters were measured. Gallstones were found in 20.5% of the family group and in 9.0% of the control group. Gallstones were found in 22.8% of the female and 16.7% of the male family members as opposed to 10.3% of the female and 8.0% of the male controls. All these differences were statistically significant. Known risk factors, such as Ashkenazi community group, higher age, and overweight, were more frequent in the control group, as were blood glucose and cholesterol. These findings strengthen the validity of the twofold higher frequency of gallstones found in the family group and are likely to be due to genetic factors. A formal genetic family study of gallstone disease is now indicated, using the ultrasonic method.