Normal mouse spleen cells treated with sodium periodate for 10 min at 4 degrees are stimulated to undergo blastogenesis and to incorporate thymidine. In contrast, periodate treatment does not stimulate DNA synthesis in nude mice spleen cells. The effect of such treatment on the antibody response in vitro induced by sheep red blood cells (SRBC) and by trinitrophenyl polyacrylamide (TNP-PAA), a T-independent antigen has been evaluated. Periodic-induced proliferation is accompanied by a marked inhibition of the immune response to both of these antigens in normal mouse spleen cells. Mild oxidation of nude cells with periodate markedly enhances their anti-TNP response elicited by TNP-PAA. The data suggest that periodate-induced immune suppression is associated with T lymphocytes. Furthermore, periodate-treated cells are capable of suppressing the in vitro antibody response of untreated normal cells.