In order to define the new human histocompatibility antigens, we have generalized primed lymphocytes using responder and stimulator cells matched for all recognized HLA-linked histocompatibility antigens (A,B,C,D,DR,MB). Many such primed lymphocytes give highly discriminatory proliferative responses specific for antigens which differ between HLA-A,B,C,D,DR, and MB matched restimulating cells. Five distinct antigens have been defined which appear to be part of a single segregant series (designated "SB"). Studies in a DR/GLO recombinant family indicate that the antigens are coded by an HLA-linked gene telomeric to GLO. Family studies of 57 HLA haplotypes provide an estimate of genotype frequency which is 12% or less for four of the SB alleles but approximately 50% for the most common (SB4, which may be a "public: determinant); approximately 25% of haplotypes are blank. Population studies of one of the SB antigens (SB1) suggest that it is in linkage disequilibrium with the SB antigens are part of a highly polymorphic new segregant series of B cell alloantigens encoded by a gene that maps between HLA-B and GLO.