CD146, also known as S-endo-1, P1H12, Mel-CAM, and MUC18, is a well-described adhesion marker of endothelial cells, which has also been identified on a limited number of other cell types, but not in fresh peripheral blood lymphocytes from healthy individuals. 1, 2 Due to its presumed specificity, the expression of CD146 has been used as the sole criterion to identify circulating endothelial cells (CECs), and has been widely used to isolate these cells from peripheral blood (reviewed in Blann et al3 and Khan et al4). In contrast, our flow cytometric studies of peripheral blood have routinely detected CD146 leukocytes. In fresh peripheral blood specimens from 10 healthy individuals stained with a panel of monoclonal antibodies to leukocyte antigens and analyzed by flow cytometry, CD45 CD146 cells were consistently identified as 1% or less of the mononuclear cells. Table 1 and Figure 1 illustrate the expression of CD146 found on lymphoid subsets. Phycoerythrin-conjugated CD146 (clone p1H12) obtained from Becton Dickinson Biosciences (San Jose, CA) and from Chemicon (Temecula, CA) yielded similar results. The CD3, CD146 cells also expressed CD2, CD5, and CD7, confirming that these cells were T lymphocytes. The use of pulse width measurements eliminated the possibility that these cells were doublets of CECs and T cells, and the use of a viability stain (7-aminoactinomycin D [7-AAD]), as well as isotype controls, excluded the possibility that this staining was due to nonspecific binding of the monoclonal antibodies. Washing peripheral blood mononuclear cells, as well as whole peripheral blood, with phosphate-buffered saline (PBS) twice prior to staining revealed no change in the percentage of T cells positive for CD146 or in the intensity of CD146 staining, thus eliminating the possibility that the lymphoid CD146 was due to binding of soluble CD146.