Contact sensitivity to 2, 4-dinitro-1-fluorobenzene (DNFB) in mice could be rapidly and specifically suppressed by a single i.v. injection of DNBSO3 just before the elicitation skin test. The effects of desensitization were also demonstrated in vitro by the diminished response of cultured desensitized lymph node cells to specific antigenic stimulation (DNBSO3). The effect was dependent on the dose of DNBSO3 injected, and it occurred immediately and disappeared within 2 days. We believe that the mechanism is a functional defect of antigen-reactive cells which have been triggered to proliferate by the desensitizing antigen. These rapidly cycling cells may not migrate properly or respond adequately to the skin test challenge and are also refractory to additional antigen stimulation in vitro. The mechanism so postulated is derived from the finding that there was an inverse relation between the proliferative rates of the cells and their degree of specific reactivity to antigen. When the desensitizing antigen raised the proliferative rate of lymph node cells, the specific reactivity of both the whole animal and of the isolated lymphoid cells was low and vice versa.