The properties of the cardiac effects of histamine on the isolated heart muscles of the Japanese monkey (Macaca fuscata) were investigated. Histamine had a concentration-dependent positive inotropic effect on left atria and papillary muscles and a positive chronotropic effect on right atria. Histamine increased the levels of cyclic AMP and shortened the duration of the action potential in Purkinje fibers, measures of its biochemical and electrophysiological effects. All of these effects of histamine were blocked by 10(-5) M cimetidine. These results indicate that histamine H2-receptors mediate the cardiac effects of histamine on the monkey heart. Histamine (10(-5) M) also restored the action potentials and contractility of K+-depolarized preparations. These effects were inhibited by verapamil (10(-6)-10(-5) M) but not by TTX (10(-5) M), suggesting that, in the monkey heart, histamine may act by increasing the slow inward current.