Histamine-induced electrophysiological effects have been investigated in guinea-pig left atria, papillary muscles and rabbit AV-nodal preparations by means of intracellular recording of action potentials, slow responses in the presence of 27 mmol/l (K+)o and voltage clamp experiments. Differentiation of the H-receptor subtypes was performed by the use of the H2-selective agonists dimaprit and impromidine and the H1- and H2-selective antagonists dimetindene and cimetidine, respectively. The following results were obtained: Histamine and the H2-agonists dimaprit and impromidine show similar actions on electrophysiological parameters of ventricular myocardium. Histamine at concentrations less than 1 mumol/l leads to a small increase in APD30 and APD90, but to a marked decrease at concentrations greater than or equal to 1 mumol/l, whereas Vmax, resting potential and amplitude remain nearly unchanged. The effects on ADP are completely blocked by cimetidine and not changed by dimetindene. Changes in action potential may be explained by an increased in slow inward current and outward currents as shown by voltage clamp experiments. In left atria histamine increases APD30 and APD90, whereas there is only a minor increase in amplitude with no changes in Vmax and resting potential. These effects are completely reversed by the H1-antagonist dimetindene but not by cimetidine. IBMX decreases APD90 and does not potentiate the action of histamine. Vmax of slow responses is increased in left atria by stimulation of H1-receptors and in papillary muscles by stimulation of H2-receptors. The results suggest that stimulation of atrial H1-receptors directly causes an increase in Ca-channel conductance.(ABSTRACT TRUNCATED AT 250 WORDS)