The genes controlling the immune response to the random linear terpolymers GAT and GLpro have been mapped in the Ir-1A or Ir-1B subregions with five lines of H-2a/H-2a recombinant mice. The I region also contains a third subregion, I-C, which codes for a lymphocyte-activating determinant, Lad2, controlling mixed lymphocyte reactivity. The mixed lymphocyte responses associated with I-C region disparity are compared with the stimulation noted with other H-2 region differences. Unidirectional lymphocyte activitation was associated with the Lad2 determinants in selected combinations.