Electrophysiological investigations of histamine in different cardiac tissues have led to the following results: Histamine and the H2-agonists dimaprit and impromidine show similar actions on electrophysiological parameters of ventricular myocardium (especially a decrease in action potential duration), which are completely blocked by cimetidine and enhanced by the phosphodiesterase inhibitor 1-methyl,3-isobutylxanthine (IBMX). These effects may be explained by an increase in cellular cAMP leading to an increase in slow inward current and outward currents as shown by voltage clamp experiments. Histamine in contrast to IBMX increases action potential duration at 90% repolarization (APD90) in atria. Histamine effects in atrial myocardium are completely reversed by the H1-antagonist dimetindene. Stimulation of atrial H1-receptors is suggested to directly cause an increase in Ca-channel conductance independent of intracellular cAMP content. Histamine reduces AH-interval, increases V max of NH-cells and may induce AV-node arrhythmias (at concentrations greater than or equal to 3 mumol/l). These effects remain unchanged by dimetindene, but are reversed by cimetidine. The results indicate that histamine increases AV-nodal conduction via H2-receptors. Unspecific membrane actions of cimetidine are not observed up to 100 mumol/l. Dimetindene increases action potential duration (APD) in left atria and decreases Vmax at concentrations greater than or equal to 10 mumol/l. However, H1-antagonistic actions of dimetindene are already observed at concentrations 1,000 to 10,000 times lower (pA2-values 8.39-9.12) so that unspecific membrane actions are suggested not to occur on a therapeutic dose level.