Complex interactions appear to exist between the renin-angiotensin system and sympathetic neurotransmission, and sympathetic activity may influence local angiotensin II formation. Arterial and forearm venous plasma levels of angiotensin I and II were therefore studied in 11 healthy males at rest during sympathetic activation elicited by mental stress, and during adrenaline induced vasodilation. Specific assays for angiotensin-(1-8) octapeptide and for angiotensin-(1-10) decapeptide (i.e. angiotensin II and I, respectively), were used. Special precautions to minimize ex vivo formation and/or degradation of angiotensins were employed. Mental stress increased regional noradrenaline overflow three-fold, with a concomitant three-fold increase in forearm blood flow, whereas intravenous adrenaline infusion increased forearm blood flow two-fold and noradrenaline overflow four-old. There was a constant positive veno-arterial concentration difference for angiotensin I under all conditions tested, compatible with local angiotensin I formation. We found no veno-arterial concentration difference for angiotensin II or regional net angiotensin II overflow under the conditions tested. These results in the forearm circulation support previous animal experimental evidence in skeletal muscle and provide no evidence in favour of a de novo formation of angiotensin II in skeletal muscle in vivo during basal conditions. Furthermore, sympathetic nerve stimulation does not seem to enhance angiotensin II generation importantly in this vascular bed.