A/Jax mice treated for I week with rabbit antiserum to A/Jax lymphocytes showed peripheral lymphopenia and tissue lymphocyte depletion which persisted for 4 weeks after initiation of serum treatment. During this time, such animals showed depression of the humoral antibody response and inability to reject skin allografts. After 4 weeks, mice recovered from effects of serum treatment. Normal blood and tissue lymphocyte levels returned, and immunologic competence was restored. Thymectomy of A/Jax mice (8 to 10 weeks old) prior to serum treatment resulted in peripheral and tissue lymphopenia and depression of antibody formation, which persisted twice as long as that shown by animals given serum alone. Similarly, skin allografts survive two to four times longer in serum-treated thymectomized mice, and, in some cases persisted over 100 days in perfect condition.