Human peripheral blood lymphocytes (HPBL) were examined for the presence of cryptic Thomsen-Friedenreich (TF) antigens as detected by PNA or an anti-TF mAb (49H8) after neuraminidase treatment of the cell surface. Neither PNA nor the mAb bound to the cells before treatment with neuraminidase. After removal of surface sialic acid, all lymphocytes were PNA-reactive, and 85% of HPBL reacted with the mAb 49H8. Seventy-seven percent of nylon wool (NW)-eluted T cells (96% Leu 1+), 80% of enriched helper T cells (83% Leu 3a+), and 78% of suppressor/cytotoxic T cells (63% Leu 2a+) carried the cryptic TF determinant recognized by the mAb 49H8. Ninety-one percent of NW-adherent cells (68% Leu 10+, 5% Leu 1+) were also TF positive. In contrast to NW-eluted T cells which showed low to moderate mAb 49H8 binding, 48% of NW-adherent cells revealed strong binding of anti-TF mAb. With progressive activation of T cells by PHA, binding of mAb to the cryptic TF antigen completely disappeared on blast cells. The presence of TF antigens on small cells in the culture was only poorly affected. The same was observed for activation of B cells with PWM. On the other hand, binding sites for PNA did not change during blastogenesis. The disappearance of the particular, mAb 49H8-reactive TF antigen on T blast cells is not due to the loss of antigen in a distinct T cell subset, but occurs to an equal extent in the helper and suppressor/cytotoxic T cell subpopulations. Thus, the majority of peripheral T and B lymphocytes carries cryptic TF antigens. Activated T or B cell blasts, on the other hand, are deficient for the particular TF antigen detected by the mAb 49H8. We interpret these data as a modulation of certain TF antigens on effector cells in the course of lymphocyte activation.