Summary: Inbred Fischer rats, rendered tolerant to rabbit Ig G, were injected daily with rabbit anti-rat lymphocyte globulin (ALG) for periods up to 1 month. These rats developed “wasting disease,” which included a hemolytic anemia. Histologically, lymphoid tissues demonstrated profound lymphocyte depletion with marked reticulum cell and moderate plasma cell hyperplasia. Animals not tolerant to rabbit Ig G required larger and more prolonged injections of ALG to produce persistent lymphopenia. Compared with the tolerant rats, weight loss was slight, “wasting disease” did not develop, and the histologic changes were minimal. Unlike the tolerant animals, these rats developed circulating antibodies against rabbit Ig G. These findings suggest that the effects of antilymphocyte globulin were potentiated in the tolerant rats, and that the reduction in lymphoid mass in these animals was greater. They provide additional evidence that “wasting disease” results whenever the lymphoid mass is reduced below a critical level irrespective of the manner employed to produce this effect.