Evidence from animal studies suggests that centrally acting opiates and opioid peptides increase catecholamine (CA) plasma concentrations, reflecting a central activation of sympathetic outflow. We describe here similar opiate actions in humans. Increasing doses of the potent mu opioid receptor agonist fentanyl (FE), 0.1, 0.2, and 0.25 mg/70 kg body weight (bw), induced a significant, dose-dependent increase of noradrenaline (NA) and adrenaline (A) plasma concentrations in healthy male individuals. Whereas NA increased continuously with increasing FE dose, a maximum A response was already reached at the lowest dose. These dose-related NA and A response patterns, showing a higher A sensitivity to opiate receptor stimulation, corresponded closely to those reported from animal studies. Furthermore, comparing the CA releasing potency of 0.2 mg FE/70 kg bw to analgetically equipotent doses of the less selective mu opioid receptor agonist morphine and the kappa agonist/mu antagonist nalbuphine in different groups of male individuals, we found similar effects of these opiates on CA plasma concentrations. These data suggest that the opiate-induced CA release in humans is not only mediated by mu opioid receptors, but may also involve kappa opioid receptor subtypes.