The direct positive inotropic effect of histamine was studied on paced left atrial preparation from guinea pigs. Histamine (10(-8) to 10(-4) M) increased the maximum tension developed in left atria incubated at 35degreesC and driven at 2 Hz. The maximum increase in tension was 60% of that observed with norepinephrine. Metiamide (3 X 10(-5) M, a specific H2-receptor antagonist) did not alter the inotropic response of left atria to histamine. However, tripelennamine (a typical H1-receptor antagonist) competitively shifted the histamine inotropic dose--response curve to the right at concentrations from 10(-8) to 10(-7) M. Higher concentrations (3 X 10(-7) and 10(-6) M) caused little further additional shift to the right. The positive chronotropic effect of histamine on spontaneously beating atria was competitively antagonized by metiamide (10(-6) and 3 X 10(-6) M). These results demonstrate that in guinea-pig atria histamine increases myocardial contractility by an interaction with receptors closely related to classical H1-receptors while its chronotropic effect is mediated by interaction with H2-receptors.