We examined the effects of anti-Pgp-1 (CD44) antibody on the in vitro deletion of murine CD4 and CD8 single positive T cells induced by Staphylococcal enterotoxin B (SEB). Soluble anti-Pgp-1 antibody enhanced the apoptosis and decreased the proliferation of SEB-responding T cells. In contrast, cross-linked anti-Pgp-1 antibody provided costimulatory signals for the T-cell activation induced by anti-CD3 antibody. Hyaluronic acid (HA), a ligand of Pgp-1, did not affect proliferation and deletion induced by SEB, whereas it mimicked the effects of the cross-linked antibody in anti-CD3-driven proliferation. T-cell Pgp-1 surface expression after 48 hr incubation with SEB was unchanged as compared to unstimulated cells. However, when the memory T cells were established, some V beta 8+ (SEB-specific) T cells Pgp-1low became Pgp-1high, displaying a bimodal character. Moreover, the Pgp-1 increased expression correlated with an increase of Pgp-1 soluble form in the supernatant. These findings suggested that signals following the triggering of the Pgp-1 molecule are important in controlling T-cell survival.