The extravasation of normal lymphocytes from blood into tissues is controlled by adhesion molecules ("homing receptors") that mediate their interaction with endothelial cells. It is an intriguing question whether malignant cells use the same pathways for hematogenous dissemination and whether these molecules are involved in the organ-specific formation of metastasis. To analyze the migration behavior of lymphoma cells in vivo, we here used several lines and sublines which exhibit differential expression of the lymph node homing receptor L-selectin and the mucosa-specific integrin alpha4beta7. We demonstrate that the ability of the various types of cells tested to accumulate in lymph nodes within the first 24 hr after intravenous (i.v.) injection is negligible, independent of their homing receptor expression profile. Our data indicate that lymphoma cells have, in comparison with naive lymphocytes, an impaired capacity to extravasate via high endothelial venules (HEV). Instead they predominantly accumulate in lung and liver, similar to activated lymphocyte populations. Nevertheless, most of the lymphoma lines tested readily form lymph node metastases in vivo. In addition, blockade of L-selectin by continual treatment with an anti-L-selectin antibody did not prevent metastatic growth of TK-1 cells in peripheral lymph nodes. We conclude that the expression of homing receptors and a high extravasation efficiency of neoplastic cells is not a prerequisite for their dissemination into lymphatic tissue.