The cDNA sequence and serological data for HLA-B73 are reported. Anti-B73 sera are found relatively frequently, considering the rarity of the antigen. It was noted early that in some cases the antibodies in sera of multiparous women did not react with the eliciting cells (fathers) and thus all behaved as a naturally occurring antibody. We report on 18 B73 antisera found during the screening of 55,000 Danish sera. Only one of the 17 stimulators typed also had the B73 tissue type. Ten of the stimulators had antigens from the B7 CREG (B7, B22, B27, B42, B67, B73), whereas none of the responders had such tissue types. In seven cases the serum was not able to react with the stimulator's lymphocytes in a cytotoxicity assay and in four cases the stimulator lymphocytes could not deplete the anti-B73 activity from the serum in absorption experiments. The cDNA of B73 was expressed correctly in COS cells and was recognized on the cell surface by a monospecific serum. The alpha 1 alpha 2 domains of B73 are most similar to those of the HLA-B22 family. Interestingly, the alpha 3 and transmembrane domains of HLA-B73 are not standard human domains, but are most similar to the corresponding domains of some gorilla and chimpanzee HLA-B genes.