Desensitization of guinea-pigs with ovalbumin (OA) or bovine gamma globulin (BGG) induces strong specific desensitization and is associated with a non-specific energy to tuberculin--PPD. Similarly, it was found that animals receiving desensitizing injections of PPD have suppressed delayed hypersensitivity reactions to OA or BGG. PPD also induced strong specific desensitization. Cyclophosphamide (CY) given in one large dose (300 mg/kg) 3 days before immunization failed to affect the specific desensitization induced by all three antigens. However, if CY was given 1 day after immunization, it was not possible to induce specific desensitization. The induction of non-specific desensitization was prevented in all three antigen systems if CY was given either 3 days before or 1 day after immunization. Desensitization with either OA or BGG markedly suppressed the specific 4 hr Arthus reactions.