Lymphocyte adenylate cylase activity is reduced in aging man, despite unaltered beta-adrenergic receptor characteristics. To define the component of human lymphocyte adenylate cyclase which is reduced in aging, we assessed nucleotide-regulatory protein (N-protein) function by complementation of eye- S49 mouse lymphoma cells and catalytic unit activity by forskolin stimulation. Within the enzyme complex, N-protein function is unchanged, while catalytic unit activity is 3.6 fold greater in young than elderly. The decreased responsiveness to catecholamines seen in aging man may be due, in some tissues, to reduced adenylate cyclase activity, specifically, the catalytic unit of the enzyme complex.