Introduction: HLA-G is thought to play an important role in the immuological recognition of pregnancy since it is the main HLA molecule expressed on the trophoblast and it seems to display immunosuppressive properties during normal implantation and pregnancy.A 14 basepair (bp) long insertion in exon 8 of the HLA-G gene seems to decrease stability of the HLA-G transcript.We have previously found that plasma concentrations of soluble HLA-G are lower in homozygous carriers of this HLA-G14bp insertion.In theory, homozygous carriers of the HLA-G14bp insertion are at an increased risk of impaired trophoblast invasion and growth since immune protection is defect.Material and Methods: We investigated the HLA-G14bp insertion/deletion polymorphism in 301 Caucasian patients with three or more consecutive miscarriages that remained unexplained after routine anatomical, chromosomal, endocrine and autoimmune screening and in 168 Caucasian women with two or more children and no miscarriages.The HLA-G14bp polymorphisms were investigated after amplification of the HLA-G exon 8 using genomic DNA and primers GE14HLAG and RHG4.Results: In all recurrent miscarriage patients 56 (18.6 %) were homozygous for the HLA-G14bp insertion compared with 19 (11.3%) of the controls (p < 0.05).HLA-G14bp insertion homozygocity was found in 19.2% of patients with secondary recurrent miscarriage (p < 0.05 compared with controls) and 17.7% of patients with primary recurrent miscarriage (not significant compared with controls).Among the children born prior to a secondary recurrent miscarriage diagnosis, the mean birth weight was 2766.3 g in 35 children born to HLA-G14bp homozygous women, which was significantly lower than the mean birth weight of 3082.7g in the 119 children born to women who were HLA-G14bp insertion/ deletion heterozygous or HLA-G14bp deletion homozygous (p < 0.01).Conclusions: Homozygocity for the HLA-G14bp insertion seems to be associated with recurrent miscarriage and especially secondary recurrent miscarriage.In first pregnancies of patients with secondary recurrent miscarriage, maternal carriage of this HLA-G14bp genotype seems to predispose to birth of children with significantly reduced birth weight compared with children born to similar patients with other HLA-G14 bp genotypes.HLA-G14bp insertion homozygocity may affect maternal immune tolerance to the trophoblast thereby causing miscarriage or intrauterine growth restriction.