To examine putative relationships between adrenergic receptors on accessible circulating cells and relatively inaccessible extravascular catecholamine target tissues, we measured mononuclear leukocyte (MNL) and lung β-adrenergic receptors and platelet and lung α-adrenergic receptors in tissues obtained from 15 patients undergoing pulmonary resection. Plasma catecholamine concentrations were measured concurrently to explore potential regulatory relationships between the activity of the sympathochromaffin system and both intravascular and extravascular adrenergic receptors. MNL and lung membrane β-adrenergic receptor densities were correlated highly (r = 0.845, P < 0.001). Platelet α2-adrenergic receptor and lung α1-adrenergic receptor densities were not. Lung α1-adrenergic receptor densities were positively related to plasma norepinephrine (r = 0.840, P < 0.01) and epinephrine (r = 0.860, P < 0.01) concentrations; in contrast, lung β-adrenergic receptor densities were not positively related to plasma catecholamine concentrations (they tended to be inversely related to plasma norepinephrine and epinephrine [r = 0.698, P < 0.05] levels). This apparent reciprocal regulation of α- and β-adrenergic receptors by the sympathochromaffin system was only demonstrable with adrenergic receptor measurement in the extravascular catecholamine target tissue. Neither MNL β-adrenergic receptor nor platelet α-adrenergic receptor densities were correlated with plasma catecholamine levels. Thus, although measurements of β-adrenergic receptors on circulating mononuclear leukocytes can be used as indices of extravascular target tissue β-adrenergic receptor densities (at least in lung and heart), it would appear that extravascular tissues should be used to study adrenergic receptor regulation by endogenous catecholamines in humans. These data provide further support for the concept of up regulation, as well as down regulation, of some adrenergic receptor populations during short-term activation of the sympathochromaffin system in humans.