Two potential mechanisms for terminating delayed hypersensitivity (DH) reactions have been examined in desensitized guinea pigs. Lack of macrophage responsiveness to lymphokines was sought as an explanation for the reduced ability of these animals to express delayed hypersensitivity. Skin-reactive factor was injected into the skin of desensitized guinea pigs and a control group of similarly immunized animals. The resulting inflammatory reactions were similar in size and intensity in both groups indicating normal macrophage responsiveness in the desensitized state. Passive cellular transfer of DH responses to desensitized animals was markedly less successful than transfer to normal animals. However, cells from desensitized guinea pigs did transfer DH responsiveness to normal animals. These data support the concept of a humoral suppressant of cellular immunity, perhaps acting as a feedback inhibitor, produced when guinea pigs are desensitized.