Since certain cytokines may play a role in unexplained recurrent pregnancy loss (RPL) and also some cytokine gene polymorphisms may affect the level of cytokine production, the aim of the present study was to investigate the relationship between RPL and polymorphisms of the genes coding for TNF-alpha (-308 G-->A), IL-10 (-1082 G-->A), IL-6 (-174 G-->C), and IFN-gamma (+874 A-->T). Genotyping was performed in 48 RPL women and 108 ethnically matched healthy individuals. In addition, we performed a meta-analysis encompassing the present results and those from studies on the association of TNF-alpha, IL-10 and IFN-gamma polymorphisms with RPL published in the literature until December 2001. The results showed: (1) no evidence of association with IL-6 gene polymorphisms; (2) significant associations, revealed by the meta-analysis, with the high cytokine production genotypes of IFN-gamma (+874 T/T: odds ratio (OR)=1.92, P=0.04) and IL-10 (-1082 G/G: OR=1.75, P=0.03), and a trend for association with the high TNF-alpha production genotypes -308 A/A and A/G (OR=1.61; P=0.18). We believe that the associations of these genotypes with RPL are interesting not only as risk factors but also because they represent another piece of evidence that these cytokines might be important in the pathogenesis of RPL.