Among 91 index cases whose diagnosis of a genetic type of hypertriglyceridemia was based on family studies, 27% had diabetes. To determine whether the familial forms of hypertriglyceridemia and genetic diabetes mellitus are inherited together or independently, the adult first degree relatives of these propositi were investigated for the presence of diabetes. Frequency of diabetes in first degree relatives of the 25 diabetic patients with a familial form of hypertriglyceridemia was identical whether such relatives were hyperlipidemic or not (13% versus 14.7%). The frequency of diabetes in both the hyperlipidemic and normolipidemic relatives of the 66 nondiabetic hypertriglyceridemic index cases also was not significantly different from each other (6.2% versus 4.0%). These results indicate that while diabetes is frequently associated with hypertriglyceridemia, genetic hypertriglyceridemia, per se, does not carry an increased risk of diabetes. Following treatment of diabetes, elevated triglyceride levels in index cases with both familial hypertriglyceridemia and untreated diabetes returned to lower but still elevated levels resembling those of affected (hypertriglyceridemic) relatives. Thus, the interaction of untreated diabetes and a familial form of hypertriglyceridemia determines the level of plasma triglyceride in a patient with both disorders.