This aim of the study was to investigate whether human leukocyte antigen (HLA)-DQA1*0505 sharing or the maternal killer immunoglobulin-like receptor (KIR) repertoire is associated with recurrent spontaneous abortion (RSA) or repeated implantation failure (RIF). The study included 224 couples with RSA, 61 couples with RIF, 182 fertile couples, and 10 couples with successful in vitro fertilization and embryo transfer (IVF)/ET at first cycle. HLA-DQA1*0505 typing using polymerase chain reaction-sequence-specific oligonucleotide (PCR-SSO) was performed in 185 RSA (117 with alloimmune abnormalities and 68 of autoimmune etiology), 61 RIF and 182 control couples, and KIR genotyping using polymerase chain reaction-sequence-specific primer (PCR-SSP) in 167 RSA and 55 RIF cases as well as 46 RSA and 10 IVF controls. No differences in DQA1*0505 sharing were found between patients and controls. In RSA and RIF women, the ratio of inhibitory to activating KIRs was slightly lower (1.53 and 1.85 vs 2.03 in controls). The analysis of maternal inhKIR and fetal HLA-C molecule pairs showed that the 'less inhibiting' combination KIR2DL3-C1 was found in higher percentage in subfertile (mainly RIF) than in fertile couples. In contrast, the percentage of cases possessing the 'strong inhibiting' combination KIR2DL1-C2 was lower in the RSA and RIF groups in comparison with that in the control groups (17.36% vs 23.91 and 16.36% vs 40%, respectively). In women with >or= 6 implantation failures, the KIR2DL1-C2 combination was not found in any of them (P = 0.0014), and the KIR2DL3-C1 combination was not found in the control IVF group. The results oppose the suggestion that increased HLA-DQA1*0505 sharing predispose to RSA or RIF. The KIR2DL3-C1 combination (or lack of the KIR2DL1-C2 one) is associated with implantation failure.