Adipocyte plasma membranes were isolated from four patients with type la pseudohypoparathyroidism, a disease in which deficiency of the stimulatory guanine nucleotide binding protein Gshas been reported, and from controls. Stimulation of adenylate cyclase by isoproterenol was defective, whereas inhibition of forskolin-stimulated cyclase activity by N6-(phenylisopropyl)adenosine was normal. The patients had low serum FFA concentrations and developed obesity in childhood. These results suggest that pseudohypoparathyroidism 1a is connected with a blunted stimulatory response of adenylate cyclase, possibly because of low Gsactivity, and that this blunted response may lead to decreased lipolysis and to obesity.