ABSTRACT: Many studies have both supported and refuted an association between HLA antigens and reproductive performance. To clarify these discrepant results, HLA antigens from 59 couples experiencing recurrent spontaneous abortions and 79 couples with unexplained infertility were compared with 51 fertile couples. Patients with recurrent spontaneous abortions were classified as either primary (no children) or secondary (abortions after having children or stillbirths) aborters, and patients with unexplained infertility were classified as primary (never pregnant) or secondary (previously pregnant) infertiles. The amount of antigenic disparity, homozygosity, and the probability of producing a heterozygotic offspring were analyzed for each group. Significantly more disparities at combined HLA loci and at DR loci were observed when childbearing controls were compared with primary aborters. Significant disparity between controls and secondary aborters was at the DQ locus. Total homozygosity as well as homozygosity at DR and DQ loci were significantly increased among primary aborters, but not secondary aborters, and at the B locus among secondary, but not primary infertile couples. Significant association in probability of heterozygote production was seen at the DQ locus in patients with primary infertility. These results indicate that controversy involving association of HLA and reproductive performance can be explained by properly classifying recurrent spontaneous aborters and unexplained infertiles.