We wished to determine whether human lymphocytes, like their murine counterparts, show organ-specific interactions with high endothelial venules (HEV). Functional HEV-binding ability was measured by an in vitro assay of lymphocyte adherence to HEV in frozen sections of human lymphoid tissues which was adapted from rodent systems. It was found that human lymphocytes bind selectively to HEV and that, whereas mature T lymphocytes bind preferentially to HEV in peripheral lymph nodes and tonsils, B lymphocytes show preferential binding to HEV in GALT. Moreover, by analyzing the binding characteristics of T4+ and T8+ T cell populations, it was found that T8+ cells adhere preferentially to HEV in GALT and mesenteric lymph nodes and tonsil, and that T4+ cells bind slightly better to HEV in peripheral lymph nodes. The above findings indicate that organ--specific lymphocyte-endothelial cell recognition mechanisms exist also in humans, and suggest that these mechanisms play an important role in normal and pathologic lymphocyte traffic.