In order to clarify the genetic background of recurrent spontaneous abortion, the frequency of HLA-A, -B, and -C alleles was analyzed in eighty-nine patients with a history of unexplained primary recurrent abortion. The frequency of each HLA-A, -B, and -C antigen allele was calculated in patients with recurrent abortion and their husbands, and compared with the frequencies in the general population represented by 207 individuals in the Niigata district of Japan. The incidence of individuals homozygous for the HLA-A, -B, and -C alleles was also compared between the patient group and the control group. The frequency of HLA-B35 in the patient group (5 of 89, 5.6 %) was significantly lower than in the general population (40 of 207, 19.3 %) (Odds Ratio, 0.25; 95 % Confidence Interval, 0.0920.65; P < 0.005; Pc, not significant). The fre- quencies of other HLA-A, -B, and -C alleles were not significantly different between the patient group and the general population. No significant difference in the frequency of HLA-A, -B, and -C alleles was observed between the husband group and the general population. The incidence of individuals homozygous for HLA-A, -B, or -C alleles in the patient group was not significantly different from the general population. The significantly lower frequency of HLA-B35 in patients with unexplained recurrent abortion suggests that the Th2- associated immune reactions may be lacking in such patients, as it has been reported that an enhanced Th2 response in conjunction with a decreased T Th1 response is a common immune reaction in HLA-B35-positive individuals.