To investigate whether human leukocyte antigen (HLA)-G gene polymorphism is associated with reproductive failure in a Polish population, we sequenced exons 2-4 of the HLA-G gene in 58 couples with three recurrent spontaneous abortions (RSAs) in the first trimester of pregnancy and 58 fertile control couples. We identified 12 different HLA-G alleles. Neither allele was found to be associated with an increased risk of RSA in the population. HLA-G allele sharing was similar in couples with RSA and in control fertile couples. All cases and controls were also genotyped for the -725C>G polymorphisms in the promoter region and the 14-bp insertion deletion in the 3' untranslated region of the HLA-G gene. The frequencies of both variants in RSA women and control fertile women were similar. These results suggest that HLA-G gene polymorphism does not influence the risk of RSA in the Polish population, but further studies are needed in this regard.