LY195448(R) (a phenethanolamine derivative that has demonstrated cytotoxic activity against cell cultures in vitro but that exhibited a hypotensive side effect during phase I trials), its p-hydroxy and acid metabolites, and a noncytotoxic S-stereoisomer were evaluated with respect to competitive binding against the beta-adrenergic antagonist [3H]dihydroalprenolol in rat brain cortex and human cardiac tissues. When IC50 and Ki values were compared, the R-isomer of LY195448 in general was more potent than the S-stereoisomer. While LY195448(R) was about 10-fold more active than the p-hydroxy metabolite in cardiac tissues, the two compounds were nearly equipotent both in blocking the binding of radioligand to the brain and in reducing blood pressure in rats. In the cerebral preparation, the binding of the acid metabolite was weak, with its activity being equal to that of the S-stereoisomer.