Recently, it has been described that human fertility is associated with the interleukin 10 (IL10) -2849 AA genotype. Pre-eclampsia is the most common pregnancy-specific complication. In the pathogenesis of pre-eclampsia, IL10 may affect maternal intravascular inflammation as well as endothelial dysfunction. Therefore, we tested the hypothesis that pre-eclampsia is associated with genetic variation in the IL10 promoter region in a case-control study for pre-eclampsia. Women homozygous for the IL10 -2849A allele have a threefold reduced risk for pre-eclampsia compared to controls (odds ratio 0.29; 95% CI 0.10-0.83). No differences in genotype frequency were found for polymorphisms in the IL10 promoter region at positions -1082, -819 and -592. This suggests that there is a genetically determined mechanism which protects the mother against pre-eclampsia, as reflected in the lower frequency of the IL10 -2849AA genotype in pre-eclamptic women.