The effects of gold sodium thiomalate (GST) on murine spleen cells were investigated using in vitro mitogen blastogenesis techniques. Addition of GST to intact spleen cells resulted in a decreased blastogenic response to the T cell mitogen, concanavalin A (Con A). Thymidine uptake of spleen cells depleted of macrophages and cultured with Con A and GST demonstrated biphasic effects. At 2.5 pg Con A/ml, blastogenesis of macrophage depleted spleen cells was inhibited to a lesser degree than intact spleen cells; whereas, at 0.5 pg Con A/ml, the macrophage depleted spleen cells were inhibited to a greater degree than the intact spleen cells. Addition of GST at intervals ranging from 0 to 48 hours indicated that inhibition occurred within 36 hours following mitogen stimulation. These results suggest that GST inhibits early events of lymphocyte activation by direct interaction with lymphocytes.