The present study was undertaken to investigate whether core 2 O-glycans are involved in binding of resting human T lymphocytes to P- or E-selectin and in recruitment of these cells to inflammatory sites. Freshly isolated human peripheral blood T lymphocytes were incubated with P- or E-selectin-coated dishes, and expression of core 2 O-glycans by the adherent and nonadherent cells was examined using the anti-1D4 mAb, which specifically recognizes human CD43 modified with core 2 O-glycans. The results indicated that both the P-selectin/adherent and E-selectin/adherent populations were significantly enriched with ID4+ cells, as compared with the initial population. An enrichment of ID4+ cells in the P- and E-selectin/adherent populations was observed in both CD4 and CD8 T cell subsets and even in the CD45RO+ memory CD4 T-cell subset. However, the anti-1D4 mAb did not inhibit binding of human T lymphocytes to P- or E-selectin, indicating that the 1D4 antigen itself is not directly involved in selectin binding. We also found that the percentage of ID4+ cells in synovial fluid T lymphocytes of rheumatoid arthritis patients was significantly increased as compared with normal peripheral blood T lymphocytes. Taken together, our results support the notion that core 2 O-glycans, which are located apart from the ID4 antigen, are involved in binding of human resting T lymphocytes to both P- and E-selectin, and these interactions may contribute to preferential recruitment of human memory CD4 T lymphocytes to inflammatory sites, including the synovium of rheumatoid arthritis patients.