Radioiodinated Tyr-3-octreotide, a somatostatin analogue, is a useful ligand for the in vitro detection of somatostatin receptors. In this study, we have investigated the possible in vivo application of this radioligand in the detection of somatostatin receptor-bearing tumors by scintigraphy. The specific somatostatin-like biologic activity of radioiodinated Tyr-3-octreotide was confirmed in vitro: (a) radioiodinated Tyr-3-octreotide competes in the nanomolar range with specific receptor binding of somatostatin to suspended human meningioma membranes and (b) the secretion of growth hormone by cultured rat pituitary cells was similarly inhibited by iodinated Tyr-3-octreotide and somatostatin. In rats, intravenously injected 123I-Tyr-3-octreotide is rapidly cleared from the circulation mainly by the liver. Although this rapid clearance limits the amount of tracer available for somatostatin receptor-bearing tumors, the advantage of this rapid clearance is that the background level is rapidly reduced in favor of scintigraphic imaging of these tumors. Pancreatic tumors in rats were localized by scintigraphy after intravenous injection of 123I-Tyr-3-octreotide.