HLA-A and B antigens were determined in a study of 37 couples and their children with trisomy 21 Down syndrome (DS), using a standard microlymphocytotoxicity test. The comparison groups included 76 couples and their healthy children. All individuals were Caucasians from the same geographical area, and there was no history of consanguinity. The parents of children with DS did not show an association with a specific HLA antigen or haplotype. Sixteen of the 37 couples (43.24%) having children with DS share two or more antigens at the A and/or B locus. This was significantly higher than the proportion in the control group (6/76, or 7.88%). Of the 16 couples having children with DS and sharing two or more antigens, eight had a haplotype in common, in contrast with only two couples in the control group. The data suggest that sharing of parental HLA-A and B antigens may be related either to the occurrence of trisomy 21 zygotes or to prenatal survival of affected embryos and fetuses.