The interaction of propranolol with erythrocyte membranes at concentrations stabilizing intact erythrocytes against hypotonic hemolysis produced corresponding perturbations in membrane protein and particularly membrane phospholipid components as monitored by increases in the reactivity of membrane amino and sulfhydryl groups towards trinitrobenzenesulfonic acid and 5,5'-dithio-bis(2-nitro-benzoic acid), respectively. Membrane-propranolol interactions were also analyzed in terms of alterations produced in the kinetic properties of membrane enzymes. These experiments provided evidence that propranolol-induced perturbations were sufficiently generalized as to influence the activity of enzymatic processes associated with both inner and outer membrane surfaces. Configurational changes in membrane phospholipids were implicated in these effects of propranolol, which included alterations in functionally significant membrane-cation interactions, It is suggested that the findings described here may provide a basis for understanding molecular aspects of membrane stabilization in other systems.