It has been possible to induce specific immunologic unresponsiveness to protein antigens in adult guinea pigs with injections of small amounts of antigen in saline at the time of sensitization with the same antigen in complete Freund's adjuvant. Adult guinea pigs, receiving a single intravenous injection of 5 mg of human serum albumin (HSA) or bovine γ-globulin (BγG) in saline at the time of sensitization with 10 µg of the same antigen in complete Freund's adjuvant, showed depression of delayed hypersensitivity and antibody formation. The phenomenon was antigen specific and persisted for at least 8 to 16 weeks. Delayed reactivity and 7 S γ2- and macroglobulin antibody formation were suppressed more completely and for a longer time than was 7 S γ1 antibody. A similar but less persistent state of immunologic unresponsiveness was produced with one tenth the suppressing dose but not with 50 µg of antigen. Less unresponsiveness resulted when a larger sensitizing dose of antigen (1 mg) was employed. The 5-mg. suppressing dose was effective as long as 3 weeks prior to sensitization and when injected by routes other than the intravenous if administered at the time of adjuvant sensitization. The mechanism responsible for this phenomenon and its relation to other states of immunologic unresponsiveness are discussed.