We examined relationships between changes in directly recorded renal sympathetic nerve activity (RSNA) and renal and total body spillover of norepinephrine into the bloodstream (RNEs and TBNEs, respectively) in anesthetized, adrenal-demedullated rats. Intravenous infusions of nitroprusside (NP) or phenylephrine (PH) produced reflexive, dose-dependent changes in RSNA. High-doses of NP significantly increased RSNA by 90%, RNEs by 155%, and TBNEs by 268%. High doses of PH significantly decreased RSNA by 37%, RNEs by 35%, and TBNEs by 33%. Ganglionic blockade with chlorisondamine decreased RSNA by 65% (P less than 0.05), RNEs by 10%, and TBNEs by 51% (P less than 0.05). There was a significant curvilinear relationship between mean changes in RSNA and mean changes in RNEs (r = 0.99). Simultaneous in vivo measurement of sympathetic nerve traffic and regional release of norepinephrine therefore may be useful in the assessment of presynaptic actions of drugs and hormones and in the evaluation of abnormal sympathetic neurotransmission in disease states.