Data presented here describe recent attempts to understand the structural basis for H-2 function. Inbred strains differing only by point mutation in different regions of H-2Kb have proven valuable in the analysis of H-2 domain function. Evidence for the interaction between the N and C1 domains in forming allorecognition determinants and antigen interaction sites is shown. The functional role of C2 is not yet known, since no mutations have been found there, but DNA-mediated gene transfer and exon shuffling techniques should prove invaluable in addressing this issue. Ir gene-type functions of class I molecules were demonstrated. The inability of low responder mutant strains to cross-react with H-2Kb-restricted CTL suggests that these phenomena reflect the failure of virus antigen to interact with low responder H-2Kbm molecules. Thus, the mutant strains provide a valuable system for investigating class I Ir genes.