Somatostatin receptors are demonstrated in the human derived gastric cell line HGT-1. Using 125I-Tyr11-somatostatin as ligand, two classes of sites were characterized with apparent dissociation constants KD1 = 0.9 X 10(-10) M and KD2 = 4 X 10(-9) M and maximum binding capacities of N1 = 20 and N2 = 556 fmol per mg protein, respectively. These values are close to those previously reported in freshly isolated parietal cells (Reyl, F., Silve, C. and Lewin, M.J.M., Somatostatin receptors on isolated gastric cells. In S. Bonfils et al. (Eds.), Hormone Receptors in Digestion and Nutrition, Elsevier/North-Holland, Amsterdam, 1979, pp. 391-400). Somatostatin binding to the high affinity sites was partially inhibited by the non-hydrolysable guanyl nucleotide analog Gpp(NH)p and by pretreating the cells with islet activating protein (IAP). Furthermore, IAP counteracted the inhibitory effect of somatostatin on histamine stimulation of adenylate cyclase. These findings are interpreted in terms of somatostatin interaction with the 41,000 Da adenylate cyclase GTP-dependent inhibitory subunit, Ni.