19 impromidine analogous guanidines were synthetized by acid hydrolysis of the corresponding N-cyanoguanidines. The guanidines were tested on the isolated spontaneously beating guinea-pig atrium for histamine H2-receptor affinity. Lengthening the ethyl chain of cysteamine by one methylene group leads to partial agonists of decreased activity. Impromidine congeners containing a branched cimetidine side chain prove to be potent H2-agonists with maximal or near maximal response. Affinity ratios in favour of the (R)-configurated enantiomers are moderate but clearly significant. The interaction between the affinity contributing moiety and the complementary receptor area shows a lower degree of stereoselectivity than does the efficacy contributing (imidazole-4-yl)propyl substituent of impromidine and sopromidine, respectively. Homoisohistamine derivatives dramatically lose both efficacy and affinity.