Receptors for cholecystokinin (CCK), gastrin, neurotensin, somatostatin and vasoactive intestinal peptide (VIP) are over-expressed in several human tumors, where they have diagnostic and therapeutic implications. Since reports on the expression of these peptide receptors in primary gastric and colonic adenocarcinomas are either non-existent or conflicting, a detailed evaluation with particular emphasis on the tissue localization was undertaken. CCK-A, CCK-B, neurotensin, somatostatin and VIP receptors were localized by in vitro receptor autoradiography with iodinated radioligands on histological sections of surgical samples of 27 gastric and 25 colonic adenocarcinomas. CCK-A, CCK-B and neurotensin-1 receptors were found in a minority of both tumor types. Somatostatin receptors were found in 18/27 gastric and 2/25 colonic cancers. VIP receptors were found in 14/26 gastric and 23/25 colonic cancers; subtype characterization suggests VIP1 receptors. In addition, resected tumor samples contained non-malignant tissues (mucosa, smooth muscle, nerves or vessels) with high amounts of the various peptide receptors. Therefore, regulatory peptide receptors are expressed differentially in gastric and colonic cancers but also very frequently in "contaminating" non-malignant tissues. Since results using morphological techniques are superior to those using homogenates, we recommend that localization of these receptors to the tissues should always be attempted, to minimize receptor over-estimation in tumors and to prevent spurious results.