Effects of calcium antagonists and Ni2+ on the positive inotropic responses to histamine mediated by H1-receptors were investigated in left atria of guinea pigs. The preparations were electrically driven at 0.5 Hz in Krebs-Henseleit solution at a temperature of 30 degrees C unless stated otherwise. Histamine in low concentrations of 10 and 100 nmol/1 produced a monophasic positive inotropic effect, whereas in concentrations higher than 1 mumol/1 it exerted a multiphasic inotropic response composed of an initial increasing phase (initial component) and a second and late developing, greater positive inotropic phase (second component). These two components were sometimes separated by a transient decrease in developed tension. Both positive inotropic components caused by 3 mumol/1 histamine were inhibited by the H1-antagonists mepyramine, D-chlorpheniramine and diphenhydramine in a concentration-dependent manner, but not by the H2-antagonist cimetidine. Pretreatment with Ni2+ in concentrations of 0.2 and 0.5 mmol/1 preferentially suppressed the second component of the inotropic effect produced by 3 mumol/1 histamine without significantly affecting the initial component. On the other hand, the monophasic positive inotropic effect of 30 nmol/1 histamine was almost unaffected by this cation. The concentration-response curves for the positive inotropic effect of histamine were hardly influenced by Ni2+ in the range of lower concentrations of histamine, but significantly suppressed in the range of higher concentrations of the agonist.(ABSTRACT TRUNCATED AT 250 WORDS)