The release of noradrenaline (NA) together with its possible cotransmitter neuropeptide Y (NPY) was investigated in the perfused dog spleen. The splenic nerve was stimulated electrically at high frequency with bursts, which evoked a simultaneous release of both substances. Infusion of the alpha 2-adrenergic blocking agents idazoxan or hydergine enhanced the amount of NA and NPY in the venous effluent. The present results demonstrate the concomitant release of a classical neurotransmitter and a neuropeptide, and suggest that at high frequency stimulation, regulation of their release operates very similarly.