INTRODUCTION: The present case-control study was designed in order to investigate the association between plasma protein Z (PZ) levels, the intron F G79A polymorphism and unexplained pregnancy loss.MATERIALS AND METHODS: 51 women with at least two consecutive or three non-consecutive fetal losses between the 8th and 12th week of gestation and 47 apparently healthy parous women of reproductive age with no history of pregnancy loss (controls) were enrolled. Allele frequencies of the PZ intron F G79A polymorphism and PZ levels were measured.RESULTS: PZ levels (mg/L) were significantly lower in cases (mean +/- S.D. 1.28 +/- 0.56) than controls (1.97 +/- 0.76, p < 0.001) and in carriers of the A allele (1.46 +/- 0.62), compared to GG homozygous subjects (1.72 +/- 0.81, p = 0.044). A higher proportion of cases (41.2%) were PZ-deficient (<1 mg/L), compared to controls (10.6%, p = 0.001). No significant difference in the frequency of at least one A allele carriers was observed between cases (39.2%) and controls (40.4%).CONCLUSION(S): It is possible that low PZ levels are a novel risk factor for unexplained recurrent miscarriage or fetal death. The presence of the F 79A allele is associated with significantly lower PZ levels, but, in the present study, was unrelated to unexplained early pregnancy loss.