A comparison has been made of the effects of cyclophosphamide (CY) pretreatment and i.v. injection of a high dose of antigen on delayed hypersensitivity induced by proteins in Freund's incomplete and complete adjuvants. Five antigens have been studied: obalbumin (OA), bovine serum albumin (BSA) bovine gammaglobulin (BGG), DNP 5-BGG and DNP 50-BGG. A spectrum of reactivity has been detected depending upon the ability of the antigen to stimulate B-cell as well as T-cell activity. Bovine serum albumin and BGG behave as relatively weak antigens in which the T-cell response, measured by delayed hypersensityity, is easily suppressed by i.v. antigen and the B-cell modulating system, revealed by CY sensitivity, is poorly stimulated. These proteins, injected i.v., are weak stimulators of antibody-dependent Arthus reactions. On the other hand, OA, DNP 5-BGG and DNP 50-BGG behave as strong antigens, resisting suppression of the T-cell response by soluble antigen and exhibiting (in Freund's incomplete adjuvant) a strongly developed CY sensitive, B-cell modulating system. Strong Arthus reactivity is readily demonstrated following i.v. administration of these antigens. A dissociation has been demonstrated between B-cell modulation of T-cell function and unresponsiveness induced by i.v. antigen. The failure to reverse the latter type of unresponsiveness by cyclophosphamide pretreatment suggests that separate mechanisms are involved in these systems.