Arpromidine is a potent histamine H2-receptor agonist and weak NPY Y1 antagonist. In the isolated aperfused heart, arpromidine was more potent in increasing cardiac contractile force and coronary flow but less effective on heart rate and less arrhythmogenic. Arpromidine may be considered a new lead for the development of "cardiohistaminergics". In the arpromidine series the order of potency found in guinea-pig atria was in good agreement with the results from isolated perfused guinea-pig hearts. In particular, the two-fold halogenated arpromidine analogues proved to be more potent positive inotropic agents than impromidine with lower stimulating effects on heart rate and reduced arrhythmogenic properties.