Recent evidence from animal studies suggests an interaction between the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS). We sought evidence for a similar interaction in man, to determine whether this interaction is presynaptic, whereby angiotensin II (ANG II) facilitates noradrenaline (NA) release, or postsynaptic, whereby ANG II facilitates the effect of NA. In our first study, a subpressor dose of ANG II was infused and NA release stimulated by physiological tests. The haemodynamic responses and plasma NA responses to SNS stimulation were not augmented by ANG II. In the second study normal volunteers were infused with either saline, ANG II, or a combination of ANG II and NA. Analysis of variance showed that ANG II interacts synergistically with NA to increase systolic blood pressure (SBP). Plasma NA and ANG II levels were not altered by the coincidental presence of NA or ANG II. These results suggest that there is a pharmacodynamic interaction between NA and ANG II which acts synergistically at a postsynaptic site to maintain SBP.