Alpha 1- and alpha 2-adrenergic receptors are the initial recognition sites on a wide variety of catecholamine-responsive target cells. This article addresses several major questions related to subtypes, structure, signal transduction mechanisms, and regulation of alpha 1- and alpha 2-adrenergic receptors. The application of biochemical and cell and molecular biologic techniques has provided many new insights regarding alpha-adrenergic receptors. Two (and perhaps three) distinct alpha 2-adrenergic receptor subtypes have been identified, and subtypes may exist for alpha 1-adrenergic receptors as well. These multiple subtypes imply much greater diversity among alpha-adrenergic receptors than among beta-adrenergic receptors. Alpha-adrenergic receptors are membrane glycoproteins with several common structural features (including seven membrane-spanning domains with extracellular amino terminus and intracellular carboxyl terminus) that are shared with other types of membrane receptors linked to guanine nucleotide-binding regulatory (G) proteins. These G proteins appear to link alpha-adrenergic receptors to multiple effector systems, including enzymes such as adenylate cyclase and phospholipases, and ion channels. The receptors themselves are dynamic entities, the number of which is regulated as a consequence of a poorly understood life cycle. Although unproven, it seems likely that several important clinical disorders represent alterations in alpha-adrenergic receptors themselves or in the G proteins or effector systems to which these receptors couple. New tools for studying receptor structure and function should help clarify the numerous, inadequately understood issues regarding alpha-adrenergic receptors and their possible alteration in disease states.