An intercellular adhesion molecule-1 (ICAM-1)-negative RT4 transitional cell carcinoma (TCC) cell line was transduced with full-length ICAM-1 cDNA via a retroviral vector. Flow cytometry showed that a sense-oriented clone (S20) highly expressed ICAM-1 while an anti-sense clone (AS6) did not. Both S20 and AS6 bound with equal frequency (30 +/- 8.7% vs 30 +/- 9.4%) to unstimulated human umbilical vein endothelial cells (HUVECs) in cell attachment assays. However, when phorbol myristate acetate (PMA)-activated T lymphocytes, which express lymphocyte function-associated antigen-1 (LFA-1), were cocultured with tumor cells, attachment of S20 increased twofold (60 +/- 11.9%) but AS6 showed no change (32 +/- 11%). Blocking studies with anti-LFA-1 and anti-ICAM-1 monoclonal antibodies caused an inhibition of the attachment to baseline levels, demonstrating that the enhancement of S20 attachment was dependent upon the LFA-1/ICAM-1 interaction. Enhanced attachment of S20 was not inhibited by the addition of isotypic immunoglobulin G. These results suggest that LFA-1-expressing leukocytes may act as a bridge between the endothelium and tumor cells which express ICAM-1 and, thereby, enhance the potential for hematogenous metastasis.