Contractions of the rabbit mesenteric artery induced by transmural adrenergic nerve stimulation at a frequency of 8 Hz were augmented by 5-hydroxytryptamine (5-HT), quipazine, methysergide, tolazoline, histamine, angiotensin II and 4-aminopyridine. The potentiating effect of 5-HT was partly reduced by cyproheptadine and by prolonged treatment with methysergide. After treatment with a histamine H1-antagonist, chlorpheniramine, histamine failed to augment but contrarily inhibited the response. This inhibition was reversed after subsequent administration of an H2-antagonist, metiamide. These results indicate that H1- and H2-receptors mediate the potentiation and inhibition, respectively, and that the effect medicated by H1-receptors normally predominates. It seems unlikely that the potentiation by these agents is due to prevention of norepinephrine metabolism, augmentation of norepinephrine release or prostaglandin formation. It is suggested that 5-HT and histamine act on postjunctional 5-HT and histamine receptors, respectively, to modulate the transmitter effect and that norepinephrine, methysergide and tolazoline may also act through the 5-HT receptors.