Recurrent pregnancy loss (RPL) is defined as three or more sequential abortions before the 20th week of gestation. There is increasing evidence to support an immunological mechanism for the occurrence of RPL. Defective production of T helper type 2 (Th2) and/or higher production of T helper type 1 (Th1) cytokines have been reported in RPL. As cytokine gene polymorphisms may be associated with different rates of cytokine production, the aim of the present study was to investigate the bi-allelic polymorphisms in TNF-alpha -308 G-->A, TNF-beta +252 G-->A, IFN-gamma +874 A-->T genes as Th1 or pro-inflammatory factors as well as IL-4 -590 C-->T, IL-10 -592 C-->A, -819 C-->T, -1082 A-->G genes as Th2 cytokines in women with RPL compared with healthy women. A total of 139 women with RPL and 143 control women with at least two successful pregnancies were included in the study. The allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) or PCR-RFLP (restriction fragment length polymorphism) methods were used for genotyping. Results indicated a significant association between the presence of CC genotype of IL-10 -592 C-->A polymorphism and the occurrence of RPL in Iranian women (63% in women with RPL and 46% in controls; OR=0.51, 95% CI: 0.3-0.85; p<0.01). There was no significant association with other positions. It may be concluded that IL-10 polymorphism at position -592 could be a genetic factor for RPL.