The role of colchicine-sensitive and CB-sensitive events in Con A-inducible activation of spleen cells and thymocytes was investigated by exposing the cells to varying concentrations of the drugs, separately or in combination, in serum-free or serum-supplemented medium and at different stages of the culture. In the initial phase, thymocytes were much more sensitive to colchicine than spleen cells. In adequate doses, either colchicine or CB alone could completely inhibit the activation process; when both drugs were combined, the resulting effect was, as a rule, not additive. It was possible to separate the delayed spontaneous agglutination (which is a concomitant of the mitogenic effect of Con A) from activation by selectively inhibiting the former with CB. It was thus concluded that the delayed agglutination is not a prerequisite for activation to be accomplished. Following a low dose of CB which is known to inhibit cell mobility without blocking activation, agglutinates cannot form spontaneously, but do so when cell collisions are produced by mechanical forces.