AIM: To evaluate the influence of familiality on the prevalence of gallstone disease (GD) in Italy.METHODS: Families of 79 subjects with gallstones (cases) and of 79 subjects without gallstones (controls)were investigated for the presence of gallstones by ultrasonography. Index cases and index controls were matched for age, sex, and operative unit. Sixty-three and sixty-two husbands and wives of index cases and index controls, respectively, were also studied.RESULTS: Overall,the prevalence of GD was significantly higher (X2=14.52, P＜0.001) in the 202 first-degree relatives of subjects with gallstones than that in the 201 first-degree relatives of subjects without gallstones (28.6% vs 12.4%, relative risk (RR) 1.80, 95% confidence interval (CI) 1.29-2.63). In particular,prevalence of GD was significantly higher in mothers,fathers, and sisters of index cases than that in the respective family members of index controls. The highest RR was observed in mothers (RR=2.35, 95%CI 1.38-4.3).Prevalence of GD was not obviously different in brothers and also in husbands and wives of index cases and index controls. Family members of index cases did not differ from family members of control cases with respect to the most important risk factors for gallstones (age, diabetes,BMI, and number of pregnancies) with an exception of a higher prevalence of diabetes in fathers of index controls than in fathers of index cases.CONCLUSION: This study confirms that familiality plays a very important role in the pathogenesis of gallstones.