We examined the role of CD45 antigen in human B cell function, using the anti-CD45 antibody, T29/33. The addition of T29/33 to B cells inhibited the proliferative response induced by various polyclonal B cell activators in a dose-dependent manner at concentrations of 0.01 to 10 micrograms/ml. Kinetic analysis indicated that T29/33 exerted its inhibitory effect when added within the first 24 h of culture initiation during a 72-h culture period, but had little effect when added at 48 h. Pre-treatment of high-density B cells with T29/33 antibody for 48 h showed a marked inhibitory effect on the proliferative response of these B cells when they were subsequently stimulated with SAC. Antibody to CD45 appeared to block the G0(G1) to S phase transition in the cell cycle analysis by propidium iodide staining. T29/33 antibody suppressed the RNA and DNA synthesis induced by SAC stimulation in B cells. These data suggested that small resting B cells were sensitive to anti-CD45-induced suppression. T29/33 antibody also suppressed immunoglobulin synthesis in B cells, independently of its suppressive effect on proliferation. These results indicated that CD45 antigen defined by T29/33 is involved in the activation, proliferation, and differentiation signals of human B lymphocytes.