Genetic control of delayed-type hypersensitivity (DTH) to chromium chloride antigen was studied in various strains of mice. Mice with I-Ab,d,f,k,r were high magnitude responders, whereas those with I-Aq,s were low magnitude responders. Studies with recombinant strains indicate that chromium chloride DTH may be influenced by the I-A region of H-2. DTH to chromium chloride is an antigen-specific response. We further revealed that response to chromium chloride does not cross-react with response to cobalt or nickel chloride. Also, transfer experiments using lymph node cells suggest that these responses are mediated by CD4+8-, Ia-T cells.