During the past 15 years there has been a striking increase in the understanding of the molecular basis of cellular response to catecholamines. In addition to the two principal subtypes of beta-adrenergic receptors (beta 1 and beta 2), there are at least two (alpha 1, alpha 2) and very likely additional subtypes of alpha-adrenergic receptors. The discovery of guanine nucleotide binding (G) proteins as transducers of receptor occupancy to activation of second messenger systems provides a common theme in cellular regulation by catecholamines. Application of techniques such as radioligand binding and photoaffinity labeling have facilitated the direct identification, quantitation, and ultimately purification of alpha 1, alpha 2, beta 1, and beta 2 receptors. Each is a plasma membrane glycoprotein with a subunit molecular weight (without the carbohydrate portion of the glycoprotein) of 40,000 to 55,000 kDa. The recent cloning and sequencing of cDNAs for alpha 2-, beta 1-, and beta 2-adrenergic receptors has revealed that although each has a unique molecular structure, they appear to share several common features, including extracellular amino terminus, seven plasma membrane spanning domains, and intracellular carboxy terminus. The application of molecular biological techniques together with antireceptor antibodies, which will allow studies of adrenergic receptors independent of binding or functional properties, should help in answering the many unresolved questions related to activation and regulation of adrenergic receptors. Foremost among these is whether diseases such as hypertension are characterized by alterations in one or more adrenergic receptor subtypes.