Complete HLA typing including HLA—A, —B, —C, —DR (D related B cell typing), —D, mixed lymphocyte culture (MLC), and primed lymphocyte testing (PLT), together with complete red blood cell (RBC), glyoxalase (GLO), GBG (Factor B), and phosphoglucomutase 3 (PGM3) typings were performed on an informative family. The five siblings inherited the four possible combinations of parental HLA haplotypes, and two of the siblings were HLA—A, —B, —C and —DR identical. Repeated MLC testing of the family revealed positive mixed lymphocyte reactivity in all combinations. B cell typing for the DR specificities demonstrated no variation from the expected inheritance pattern and specifically no recombination event. GBC and GLO typings militated against a recombination involving the paternal chromosome. HLA‐D testing revealed that only one of the HLA—A, —B, —C, and —DR identical siblings gave typing responses to the HLA—Dw3 specificity present on that maternal haplotype. Utilizing HLA haploidentical combinations, lymphocytes were primed against the four parental haplotypes and the non‐Dw3 haplotype of interest (Aw24—B8—DRw3—LDY) in the PLT. The sibling inheriting this haplotype did not restimulate cells primed against the A2—B40—DRw6—LDY specificity. Furthermore, no discrimination was observed in the restimulation of lymphocytes primed against this haplotype. Possible interpretations of these family data include: a spontaneous mutation, non‐major histocompatibility locus