Catecholamines stimulate Na,K-ATPase activity in the microsomal membranes of the brain and brown adipose tissue. This stimulation is apparent in the absence of soluble, cytosolic inhibitors and exhibits the same characteristics in both tissues: it occurs at high concentrations (10(-6)-10(-4) M) only; there is no difference in potency between isoprenaline, norepinephrine and epinephrine (EC50 = 1-2 X 10(-5) M); the D-stereoisomer of isoprenaline is equally as effective as the L-form; stimulation of Na,K-ATPase may also be achieved by the metal chelators EDTA, EGTA and desferal; the hydrophobic beta-blockers, propranolol and alprenolol, inhibit both the norepinephrine-stimulated and basal levels of enzyme activity at concentrations of 10(-5)-10(-3) M; phenoxybenzamine, an irreversible alpha-adrenergic blocker, inhibits basal Na,K-ATPase as well as norepinephrine-stimulated enzyme activity (EC50 = 2.5 X 10(-5) M). Because none of these observations can be related to the properties of the stereospecific adrenergic receptor (alpha or beta), it may be concluded that the catecholamine-Na,K-ATPase interaction is not mediated by the receptor. More probably, catecholamines may antagonize the Na,K-ATPase inhibition caused by some tightly membrane-bound metals (but not vanadium) via the ortho-catechol moiety of the catecholamine molecule. The stimulation of brown fat Na,K-ATPase by catecholamines does not have much relevance to the norepinephrine-stimulated thermogenesis in this tissue.