The monoclonal antibody HECA-452 identifies an antigen that is primarily expressed on high endothelial venules, the preferred site of lymphocyte extravasation in lymphoid tissues, and also on a subpopulation of myelomonocytic cells and some T-cells. We investigated the expression of the HECA-452 antigen, also called the cutaneous lymphocyte associated antigen, in primary cutaneous and primary non-cutaneous T-cell non-Hodgkin's lymphomas. The tumour cells of cutaneous T-cell non-Hodgkin's lymphomas were positive in 53% of cases, while only 5% of the non-cutaneous lymphomas were positive. These differences were also present in morphologically identical tumours. Thus, the tumour cells in six out of 10 primary cutaneous anaplastic large cell T-cell lymphomas were positive, while they were positive in none of 24 primary non-cutaneous anaplastic large cell T-cell lymphomas. In general, primary cutaneous and primary nasal T-cell non-Hodgkin's lymphomas were devoid of HECA-452 positive high endothelial venules, whereas most nodal T-cell non-Hodgkin's lymphomas contained HECA-452 positive high endothelial venules. These observations suggest that the HECA-452 antigen might be related to a skin-associated type of lymphoid tissue and to lymphomas originating in the skin. However, the results of HECA-452 expression in secondary sites, and the clinical data of the primary cutaneous large cell lymphomas did not support the concept that HECA-452 is functionally involved in homing to the skin, or that loss of the HECA-452 antigen is related to tumour progression of primary cutaneous T-cell lymphomas.(ABSTRACT TRUNCATED AT 250 WORDS)