Aim of this study is to evaluate the familial risk of cholelithiasis in non hospitalized subjects with and without gallstones. A population sample of 2.472 subjects was examined by echography for gallstones; 220 subjects (92 males and 128 females) had gallstones or had already been cholecystectomized for gallstones. These cases and an equal number of controls were interrogated about the diagnosis of gallstones in their family using a standardized questionnaire. The comparison of the frequency of symptomatic gallstones and cholecystectomies for gallstones in the relatives of cases and controls showed an increase of the relative risk of gallstones in sons of parents with cholelithiasis (OR 2.9, CI 95% 1.2-8.0) and in siblings of subjects with cholelithiasis (if sister with gallstones: OR 2.4, CI 95% 1.05-5.6; if brother with gallstones: OR 2.9, CI 95% 0.6-14.6). The stratification for sex of cases and controls, however, pointed out that the risk increased only in daughters and sisters of subjects with gallstones. There was no statistically significant difference of frequency of gallstones between spouses of cases and controls (chi square, p greater than 0.05). The results of this study confirm that there is a familial risk of gallstones, even if it is evident only in the female relatives of subjects with gallstones, and suggest that probably the main cause of this risk is genetic and not environmental.