The incidence and risk factors of chlorpropamide-induced hyponatremia were assessed in diabetic outpatients. In 176 chlorpropamide-treated patients, 11 (6.3%) exhibited hyponatremia (serum sodium less than or equal to 129 meq/L) during the mean follow-up period of 7.4 yr. In contrast, only one (0.6%) developed hyponatremia in 162 tolbutamide- or glibenclamide-treated patients (P less than 0.005). Moreover, administration to elderly patients and combination with thiazide diuretics were regarded as significantly potent risk factors for the development of hyponatremia in patients receiving chlorpropamide.