Background and objectives: The functional polymorphisms regulating immunologic responses may influence the proliferation or suppression of malignant lymphoma. Polymorphism of a specific gene can have an important effect on gene transcription, the stability of the mRNA, or the quantity and activity of the resulting protein. Interleukin –1 (IL-1) gene cluster polymorphisms have been shown to be important mediators of inflammation. This study aimed to determine whether polymorphisms at IL-1 receptor antagonist (IL-1ra) locus modulate the risk of developing malignant lymphoma. Methods: the hospital-based case-control study was conducted in Epidemiology and Genetics Unit, Algernon Firth Building, University of Leeds, LS2 9JT. Genotypes were determined for a variable length polymorphism in intron 2 of the IL-1ra gene (IL-1RN) using PCR based technique. Genotypes were examined in a total of 279 lymphoma cases, 60 Hodgkin's disease (HD) cases and 464 non-cancer control subjects. Results: The overall allele distribution of these polymorphisms did not differ substantially between patients and controls; the odds ratio (OR) was 0.72 and 95% confidence interval (CI) was 0.5-1.03 for the allele 2 carriers of IL-1RN. Subgroup analysis according to histology [diffuse large B-cell lymphoma (DLBC) and follicular cell lymphoma (FCC)] failed to illustrate differences except for DLBC which showed a significant deficit of the 2/2 genotype in the older DLBC cases, i.e. that the IL-1RN*2/*2 genotype is protective for cases in the 60-65 years group compared to the 1/1 genotype (OR = 0.25 & 95% CI=0.09 – 0.67). On the other hand the IL-1RN*2/*2 genotype was a risk for HD cases (OR=2.27 & 95% CI=1.22-4.24). Conclusion: The data of this study show a limited association between IL-1 RN gene polymorphisms and malignant lymphoma risk in total. IL-1RN*2/*2 is associated with increased risk to HD. The possible protection role/risk association of the IL-1RN*2/*2 genotype and DLBC/HD respectively needs further clarification