SUMMARYThe antitumor enzyme L-asparaginase exerts an antiproliferative action against asparagine synthetase-deficient tissues by depleting circulating L-asparagine. L-Asparaginase and L-glutaminase completely suppress in vitro lymphocyte blastogenesis at doses of 0.1-1.0 international units (IU)/ml. L-Asparaginase suppresses both humoral and cellular primary immune responses including organ allograft rejection in vivo. Since this enzyme is immunosuppressive and not myelosuppressive, its use in man should be considered in the preventive therapy of organ allograft rejection. Also, the finding that specific amino acid depletion is immunosuppressive should encourage investigation of the amino acid requirements of lymphoid tissue and other approaches to amino acid depletion or antagonism in chemical immunosuppression.