Mouse lymphocytes were cultured with phytohemagglutinin or concanavalin A and at various times antiserum to each mitogen was added. Incorporation of thymidine was partially inhibited even when antisera were added after 48 hr. Quantitative analysis of the inhibition produced in normal cultures or cultures containing colchicine suggested that the inhibition observed could not be explained simply by prevention of activation in the first division cycle. This was confirmed in other experiments where tritium-labeled cells were prevented from entering a second division cycle by specific antiserum. It is concluded that the continued presence of these mitogens is required to initiate division cycles beyond the first activation and that lymphocyte transformation is thus not an irreversible derepression leading to repetitive cell divisions.