Interleukin-10 (IL-10) is mainly an anti-inflammatory cytokine produced by a number of cells including normal and neoplastic B cells. It has been implicated in autoimmunity, transplantation tolerance and tumourigenesis. Polymorphisms in the IL-10 gene promoter genetically determine inter-individual differences in IL-10 production. The aim of this study was to determine whether polymorphisms in the IL-10 gene promoter play a role in predisposing an individual to lymphoma. We analysed the frequencies of three single base substitutions in the IL-10 promoter in patients with aggressive lymphoma (B-cell DLCL n = 46, other aggressive histologies n = 17), Hodgkin's disease (n = 44) or low/intermediate grade lymphoma (n = 46), compared to healthy controls. The frequency of the low-IL-10 producing AA allele (at position -1082) was significantly higher in patients with aggressive lymphoma compared to controls (p = 0.0344, Odds ratio 1.974, 95% C.I 1.066-3.655). Similarly, the frequency of the low IL-10 producing ATA or the intermediate-IL-10- producing ACC haplotype was significantly higher in patients with aggressive disease compared to controls (p = 0.0255, Odds ratio 1.647, 95% C.I 1.077-2.518). No association was found between IL-10 genotypes and Hodgkin's disease or less aggressive forms of lymphoma. Thus, polymorphisms in the IL-10 gene promoter which are associated with a low IL-10 producing phenotype may influence susceptibility to aggressive forms of lymphoma or may contribute to the pathogenesis of this disease.