Experiments were performed to examine the interaction(s) between alpha 1-adrenergic and S2-serotonergic receptors of vascular smooth muscle of the dog. Rings of isolated coronary and femoral arteries (without endothelium) were suspended for isometric tension recording in organ chambers filled with modified Krebs-Ringer bicarbonate solution. 5-Hydroxytryptamine (serotonin) augmented the responsiveness to norepinephrine in the coronary artery (log shift at ED50 of the concentration-response curve: 2.9-fold). In the femoral artery, the contractions to either norepinephrine or the partial alpha 1-adrenergic agonist St 587 were unchanged by serotonin. Ketanserin (10(-9) M) augmented the response to the full alpha 1-adrenergic agonist phenylephrine, but not to that of St 587; at 5 x 10(-9) M, it depressed the contractions to phenylephrine. Ketanserin did not affect the alpha 1-adrenergic blocking properties of prazosin. By contrast, prazosin, in a concentration selective for alpha 1-adrenergic receptors, potentiated the inhibitory effect of ketanserin on contractions evoked by serotonin. These experiments suggest different interactions between S2-serotonergic and alpha 1-adrenergic receptors in the canine coronary and femoral artery.