Allografts can be rejected as a result of major histocompatibility antigen disparity or as a result of differences at any of a number of minor histocompatibility antigens. In many cases, rejection due to multiple minor histoincompatibility is as difficult to control as that induced by major histoincompatibility. Although an understanding of the molecular, biochemical, and functional parameters of the major histocompatibility loci and their products is increasing at an exponential rate, little is known about these same facets of minor histocompatibility loci and their products. It is generally accepted that minor histocompatibility loci in the murine model have a degree of polymorphism similar to that of H-2K or H-2D. This conclusion was based on typing alleles by the classic F1-skin graft test. Based on these allelic assignments, numerous unexpected findings of CTL specificity were made. Therefore, a systematic analysis was made comparing CTL specificity, F1-complementation, and allograft rejection. Based on these three parameters, the data presented using strains of mice that were bred to, and therefore presumed to, differ only at H-3 indicate that the antigen disparity of these congenic strains and the parental B10 strain as defined by CTL specificity and skin graft rejection is much more complex than originally described. One especially interesting chromosomal region is H-3/beta 2-microglobulin in the fifth linkage group of chromosome 2. Using CTL, ten specificities are defined, three of which appear to be specific for beta 2-microglobulin-A, -B, and -C. These findings raise the question of whether any minor histocompatibility locus is polymorphic or is instead a composite of multiple minor H-loci which are masquerading as a single locus.