CD137 (ILA/4-1BB), a member of the tumor necrosis factor receptor family, and its ligand are expressed on activated T lymphocytes and on antigen-presenting cells, respectively. Via bidirectional signal transduction, this receptor-ligand system regulates the activation, proliferation, and survival of T and B lymphocytes and monocytes. We used immunohistochemical studies on human tissue samples to determine in vivo CD137 expression in nonimmune tissue samples. Strong CD137 expression was found in blood vessel walls, on the endothelial layer, and on the vascular smooth muscle cells. But in 32 healthy tissue samples examined, none contained CD137-positive vessels. Also, in benign tumors (2/14) and in inflammatory tissues (2/9) only a minority had CD137-expressing vessels. However, malignant tumors had a significantly enhanced frequency of CD137-expressing blood vessels (11/34).