In vitro receptor measurements in tumors were performed to evaluate the potential of the vasoactive intestinal peptide receptor (VIP-R) as an imaging tool in human cancer. METHODS Three hundred thirty-nine human tumors were investigated for their VIP-R content by in vitro receptor autoradiography on tissue sections with 125I-VIP. For comparison, somatostatin receptors (SS-R) were measured in adjacent sections of these tumors with 125I-[Tyr3]-octreotide. RESULTS VIP-R were characterized and localized in the neoplastic cells of most breast carcinomas, breast cancer metastases, ovarian adenocarcinomas, endometrial carcinomas, prostate cancer metastases, bladder carcinomas, colonic adenocarcinomas, pancreatic adenocarcinomas, gastrointestinal squamous cell carcinomas, non-small-cell lung cancers, lymphomas, astrocytomas, glioblastomas and meningiomas. Among neuroendocrine tumors, all differentiated and one-half of undifferentiated gastroenteropancreatic tumors, pheochromocytomas, small-cell lung cancers, neuroblastomas and inactive pituitary adenomas were found to express VIP-R. In general, VIP-R were found much more frequently than SS-R, but only 5 of 19 growth hormone-producing adenomas and no medullary thyroid carcinomas or Ewing sarcomas had VIP-R. In all tumors tested, the VIP-R were of high affinity and specific for VIP and pituitary adenylate cyclase-activating peptide. No cross-competition between VIP and SS could be identified. CONCLUSIONS Most human carcinomas express VIP-R, as measured by in vitro receptor autoradiography. These data represent the molecular basis for evaluation of VIP-R imaging of these tumors in vivo and predict its great potential value.