The possibility that sympathetic nervous system activity may be altered in Brattleboro rats with diabetes insipidus (DI) was studied using the norepinephrine (NE) turnover technique. Female DI and Long-Evans rats were used. NE turnover in peripheral organs was calculated by measuring the decline in tissue [NE] after inhibition of tyrosine hydroxylase with alpha-methyltyrosine. NE turnover was increased significantly in the kidney of DI rats but was not significantly altered in other peripheral organs examined (heart, duodenum, skeletal muscle). Both NE and epinephrine concentrations in the adrenal gland were significantly higher in the DI rats. Treatment of DI rats for 7 days with vasopressin tannate (Pitressin, 100 mU/100 g) or 1-deamino-[8-D-arginine] vasopressin (DDAVP, 250 ng X kg-1 X day-1) reversed the changes in renal NE turnover and also decreased the turnover in other tissues. The results of these studies suggest that, compared with Long-Evans rats, DI rats have a selective increase in NE turnover in the kidney and the potential to release more catecholamines from the adrenal glands. The apparently nonspecific effect of antidiuretic therapy on NE turnover in DI rats is probably mediated by the epithelial receptor for vasopressin, because both Pitressin and DDAVP produced similar results.