Kidney stones develop more frequently in individuals with a family history of kidney stones than in those without a family history; however, little information is available regarding whether the increased risk is attributable to genetic factors, environmental exposures, or some combination. In this report, the relation between family history and risk of kidney stone formation was studied in a cohort of 37,999 male participants in the Health Professionals Follow-up Study. Information on family history, kidney stone formation, and other exposures of interest, including dietary intake, was obtained by mailed questionnaires. A family history of kidney stones was much more common in men with a personal history of stones at baseline in 1986 than in those without a history of stones (age-adjusted prevalence odds ratio, 3.16; 95% confidence interval [CI], 2.90 to 3.45). During 8 yr of follow-up, 795 incident cases of stones were documented. After adjusting for a variety of risk factors, the relative risk of incident stone formation in men with a positive family history, compared with those without, was 2.57 (95% CI, 2.19 to 3.02). Family history did not modify the inverse association between dietary calcium intake and the risk of stone formation. These results suggest that a family history of kidney stones substantially increases the risk of stone formation. In addition, these data suggest that dietary calcium restriction may increase the risk of stone formation, even among individuals with a family history of kidney stones.