American blacks and whites show heterogeneity in serologically detected and lymphocyte-defined HLA-D region antigen frequencies. Also, alterations in linkage relationships are seen in DR and DQ specificities. Since homozygous typing cells probably identify a cluster of specificities that are usually found in linkage disequilibrium in a given population, it is not surprising that blacks have unique HLA-D types. The significance of the observed differences in the function of class II molecules is being investigated.