An association of the phosphoglucomutase locus 1 (PGM 1 ) genetic polymorphism with repeated spontaneous abortion (RSA), with intrauterine development in both normal and diabetic pregnancies, and with fertility has been reported in previous studies. In view of the evolutionary interest and of a possible clinical relevance of PGM 1 selection during intrauterine life, this study considers healthy puerperae, consecutive newborns, and couples with RSA as well as two alleles (PGM 1 *1 and PGM 1 *2). The joint maternal-neonatal PGM 1 distribution in a sample from an Italian rural population is significantly different from that expected assuming Hardy-Weinberg conditions for equilibrium. Deviation is dependent on maternal age and parity. The joint mother-newborn PGM 1 genotype distribution is significantly associated with a positive history of previous spontaneous miscarriage, suggesting that the presence of the PGM 1 *2 allele in the father predisposes to spontaneous abortion. This hypothesis is also supported by the observation that in couples with RSA, the delivery of a live born infant within 5 years from the first episode of miscarriage is negatively associated with the presence of a PGM 1 *2 allele in the husband. Altogether these observations suggest the hypothesis of PGM 1 maternal selection at the reproductive level involving a differential role of PGM 1 *1 and PGM 1 *2 alleles of paternal origin.