An attempt has been made to elucidate the factors responsible for the ability of heterologous anti-lymphocyte plasma (ALP) to depress lymphocyte counts when injected into an animal of the same species as that which provided the lymphocytes for immunization. The results suggest that ALP depresses lymphocyte counts by virtue of its content of antibody directed against antigenic moieties which are contained in lymphoid cells and which are distinct from the individual and species specific antigens of the animal. The results also indicate that the ability of ALP to produce a lymphopenia is, to a significant degree, dependent on normal adrenal function in the recipient of the plasma. In addition, the findings reported in this communication confirm previous observations (5f 6) which indicated that the immunosuppressive potency of ALP could not be correlated with either its content of agglutinating and cytotoxic antibodies directed against lymphocytes or its ability to depress lymphocyte counts. © 1968 by The Williams and Wilkins Co.