In five patients with Bartter's syndrome, mean (±SE) plasma norepinephrine concentrations increased from 324 ± 75 pg/ml with the patients in the supine position to 550 ± 100 pg/ml, 753 ± 104 pg/ml and 808 ± 116 pg/ml after 2,5 and 10 minutes, respectively, in the standing position, levels significantly higher than normal. Plasma epinephrine concentrations were indistinguishable from normal. One patient was shown to be resistant to the pressor (but not the metabolic) effects of intravenously administered norepinephrine prior to treatment with reversion to normal pressor responsiveness during indomethacin administration. Similarly, that patient's exaggerated endogenous norepinephrine response to standing (10 minute plasma value of 1,110 pg/ml) reverted to normal (10 minute value of 462 pg/ml) during indomethacin administration. Thus, patients with Bartter's syndrome exhibit a hyperadrenergic state consistent with resistance to endogenous, as well as exogenous, norepinephrine. Since the metabolic responses to intravenously administered norepinephrine were normal in the patient studied, norepinephrine resistance would appear to be limited to the vascular system. Reversion of norepinephrine resistance during administration of an inhibitor of prostaglandin synthesis suggests that this hyperadrenergic state is not a primary pathogenetic abnormality in Bartter's syndrome.