Introduction: Extravasation and tissue infiltration of leukocytes and metastatic tumor cells requires the regulated expression and function of adhesive and pro-proteolytic surface molecules.Materials and Methods: In an attempt to identify novel activation associated T cell surface receptor structures, we raised a series of monoclonal antibodies against HUT102 cell surface structures. Two of these antibodies (541-10B2 and 541-2E5) fulfilled the set criteria of clear-cut reactivity with HUT102 cells and with in vitro activated peripheral blood T lymphocytes and no or minimal reactivity with freshly isolated peripheral blood leukocytes.Results: We demonstrate here, that human T cells upon activation neo-express the melanoma metastasis associated surface molecule CD146 (MUC18/MCAM). The specificity of our mAbs for CD146 (MUC18/MCAM) was revealed by (i) definition of appropriate molecular mass of approx. 110 kDa, unreduced, 120 kDa, reduced, (ii) reactivity of mAbs with CD146 (MUC18/MCAM) cDNA transfected mouse L-cells, (iii) conclusive cross-wise immunoblotting experiments with CD146 (MUC18/MCAM) specific mAbs, and (iv) by N-terminal amino acid sequencing of precipitated protein. In vitro activation by PHA caused neo-expression of CD146 (MUC18/MCAM) on PB-T cells within one day of stimulation reaching a maximum on day three. In vivo expression of CD146 (MUC18/MCAM) was confirmed on CD3 + T cells infiltrating delayed type hypersensitivity lesions of the skin, on synovial fluid T cells of rheumatoid arthritis patients and on distinct T leukemia cells. CD146 (MUC18/MCAM) cell surface expression on activated T cells is mirrored by the presence of specific mRNA. Leukocytes of healthy donors do not show significant CD146 (MUC18/MCAM) expression.Conclusion: The finding that CD146 (MUC18/MCAM) is also expressed on activated T cells might suggest that this adhesion molecule is involved in the extravasation and/or homing of activated T cells.