A C-T substitution at position 590 in the interleukin-4 (IL-4) gene is associated with increased production of IL-4. We sought to determine the associations between this polymorphism and susceptibility to brucellosis. DNA was extracted from the whole blood of 163 control individuals and 282 patients with brucellosis. A polymorphism in the IL-4 gene at position 590 from the promoter site was determined using an allele-specific PCR method. The prevalence of the T allele of IL-4 polymorphism was significantly higher in the patients group than in controls (28.9% vs 11.4%, p<0.004). Patients with brucellosis had a higher frequency of intermediate producer genotype (CT) (53.5% vs 22.7%, p<0.001) while low producer genotype (CC) was higher in the control group (77.3% vs 44.4%). Multiple logistic regression analysis demonstrated that patients who were heterozygous (CT) for interleukin-4 promoter polymorphism had a significantly higher risk for brucellosis with an odds ratio of 4.2 (95% CI 2.7-6.6, p<0.0001). Our findings demonstrate for the first time an association between IL-4 590 promoter polymorphism and contracting brucellosis in the Iranian population.