SUMMARYThe present study tests the effect of amantadine upon the response of sensitized lymphocytes in vitro to specific antigen. Amantadine specifically inhibited tritiated thymidine incorporation, blast transformation, and cell proliferation of sensitized cells exposed to specific antigen. Unlike other immunosuppressive agents, this chemical appears to affect only the proliferative response of cells in systems relating to immunological recognition. Phytohemagglutinin (PHA) stimulation of the same cell population is enhanced by amantadine. It is postulated that amantadine exerts its effect through preferential hydrophobic binding to lipids which integrate immunoglobulins and transplantation antigens into the lymphocyte membrane.