Somatostatin receptors were detected in peritumoral veins of various human cancer tissue specimens. Vascular and neoplastic tissue from 14 colonic adenocarcinomas, 13 carcinoids, 6 renal-cell carcinomas and 7 malignant lymphomas were analyzed for somatostatin receptors by use of quantitative receptor autoradiography. In colonic carcinoma specimens, the peritumoral vessels expressed a high density of somatostatin receptors, whereas the neoplastic tissue itself was receptor-negative in many cases. In contrast, the incidence and density of somatostatin receptors in peritumoral vessels was low in well-differentiated gastrointestinal and bronchial carcinoids, in contrast to the high density of such receptors in the carcinoid tumor tissue. Autochthonous vessels surrounding other tumors such as renal-cell carcinomas or malignant lymphomas also frequently expressed somatostatin receptors. In all cases, the somatostatin receptors were localized in veins, particularly in the smooth-muscle cell layer. They exhibited specific and high-affinity binding of somatostatin-14, somatostatin-28 and octreotide, suggesting a preferential expression of the SSTR2 receptor subtype. Since the vessels of normal non-neoplastic human tissues, e.g. of intestine or lymphatic organs, have few somatostatin receptors, the increased somatostatin receptor expression in peritumoral vessels observed in this study may be linked to the neoplastic process itself. The results suggest that somatostatin and somatostatin receptors may play a regulatory role for hemodynamic tumor-host interactions, possibly involving tumor stroma generation, tumor environment, angiogenesis and, particularly, vascular drainage of poorly differentiated neoplasms.