We hypothesized that non-proliferating (quiescent) human vascular endothelial cells would not express somatostatin receptor subtype 2 (sst 2) and that this receptor would be expressed when the endothelial cells begin to grow. To test this hypothesis, placental veins were harvested from 6 human placentas and 2 mm vein disks were cultured in 0.3% fibrin gels. Morphometric analysis confirmed that 50-75% of cultured vein disks developed radial capillary growth within 15 days. Sst 2 gene expression was determined by reverse transcription-polymerase chain reaction (RT-PCR) analysis of the RNA from veins before culture and from tissue-matched vein disks that exhibited an angiogenic response. The sst 2 gene was expressed in the proliferating angiogenic sprouts of human vascular endothelium. The presence of sst 2 receptors on proliferating angiogenic vessels was confirmed by immunohistochemical staining and in vivo scintigraphy. These results suggest that sst 2 may be a unique target for antiangiogenic therapy with sst 2 preferring somatostatin analogues conjugated to radioisotopes or cytotoxic agents.