As a first step in determining the genetic control of contact hypersensitivity in mice, 2,4-dinitro-1-fluorobenzene (DNFB) was applied to induce ear swellings. Studies with congenic and recombinant inbred strains of mice revealed that the DNFB contact hypersensitivity is controlled by the I-A subregion, as well as non-H-2 regions. The results presented suggest that the major histocompatibility complex-linked immune response genes seem to be playing an important role in the contact hypersensitivity to the DNFB antigen.