HLA-G is a class I major histocompatibility complex gene that is expressed in cytotrophoblasts at the materno-fetal interface. It has been suggested that HLA-G could play a key role in materno-fetal immunological interactions during pregnancy. To investigate whether there is an association between HLA-G locus and recurrent spontaneous miscarriage, HLA-G alleles were determined by a PCR-RFLP method in 38 couples with recurrent spontaneous miscarriage and in 26 random control couples. In this series parental HLA-G sharing, extended HLA-G/A haplotypes and the frequencies of the HLA-G alleles were similar in the two groups. Thus, our data suggest that there is no detectable relation between susceptibility to recurrent spontaneous miscarriage and HLA-G locus.