The frog erythrocyte membrane provides an excellent model system for the study of beta-adrenergic receptor-adenylate cyclase interactions since it possesses an adenylate cyclase enzyme which is very responsive to catecholamines. The purpose of these studies was to evaluate directly whether the functions of receptor binding and adenylate cyclase activity are carried out by a single macromolecule or separable molecular entities. Obtaining this information is a first step in understanding at a molecular level how receptor binding is "coupled" to enzyme activation. Binding and cyclase activities were solubilized from the frog erythrocyte membrane with digitonin and were observed to partition independently during gel exclusion chromatography in the presence of solubilizing detergent. This finding documents that the beta-adrenergic receptor and adenylate cyclase enzyme are, in fact, separable macromolecules. Under the particular experimental conditions employed, the elution of beta-adrenergic receptor binding on Sepharose 6B was not altered by the absence or presence of beta-adrenergic agonist or antagonist ligands or by exposure of the membranes prior to solubulization to the guanyl nucleotide analog, guanyl-5'-yl imidodiphosphate.