A series of 1-(aralkylamino)-3-(aryloxy)propan-2-ols were synthesized, and their apparent dissociation constants (Kapp) were determined by using rat ventricular muscle (RVM) and rat lung membrane (RLM) preparations. Analysis of the binding studies suggests the existence of different modes of binding dependent on the presence or absence of the 4-substituent in the aryloxy ring and the nature of that ring. Without 4-substitution only one compound (4), bearing the 2-(2-methoxyphenoxy)ethyl substituent on the amino group, shows high cardioselectivity. Introduction of the 4-acylamido substituent into the phenoxy ring renders all compounds cardioselective. The cardioselective influence of 4-substitution is diminished or eliminated when the phenoxy ring is replaced by naphth-1-yloxy.