We are studying the interaction of cardio-active and vasoactive hormones and drugs with their cell receptors. The study consists of three interdependent phases: (1) Study of the chemical and structural properties of both the hormones or drugs and the receptors in necessary for their interaction and for activation of cell membrane enzymes. Tee distribution and function of receptors is being studied in an easily dispersed tissue leukocytes obtained from blood and spleen. This experimental approach may set the stage for studying the interaction of the same hormones and drugs with smooth muscle cells in more complex tissues, such as blood vessel, bronchial musculature, or myocardium. (2) Detailed study of cyclic AMP, an intracellular second messenger, in leukocytes. The mechanism of activation and control of ademulate cyclase by agonists and the relation of this enzyme to receptors is being investigated. Understanding the regulation of intracellular cyclic AMP will facilitate phase (3): Study of the relation of leukocyte functions to the presence of receptors and the biochemical effects produced by agonists. We hope eventually to apply our findings to man, in order to elucidate the molecular pathogenesis and pharmacologic amelioration of certain cardiovascular abnormalities including endotoxemia and cutaneous or general anaphylaxis.