Several lines of evidence point to a relevant role of IL-18 in the process of asthma. Some studies suggest that the polymorphism in the gene of IL-18 can be involved in many inflammatory and atopic diseases such as asthma. The aim of our study is to estimate the frequency of the IL-18-607 C/A (rs 1946518) promoter polymorphism in Tunisian children with asthma. We investigated whether the presence of this polymorphism -607 C/A was associated with asthma or atopy and whether this polymorphism influenced the severity of asthma in affected children. We examined also the relationship between the IL-18 gene polymorphism and the serum total IgE level. The IL-18/-607 C/A polymorphism was analysed by polymerase chain reaction and restriction fragment-length polymorphism (PCR-RFLP) analysis. A total of 105 asthma patients and 112 controls as part of the whole children population were studied in a case-control study. Among the 105 children with asthma, 40 were also studied for linkage analyses with their respective parents. We noted that the A allele was associated with statistically significant increases in the risk of asthma in the case-control study (odd ratio (OR) = 1.55, 95% confidence interval (CI) 1.03-2.33. Moreover, the A allele was also associated with atopic asthma (P = 0.008), but not with asthma severity. The transmission disequilibrium test (TDT) analysis in this family study did not suggest a preferential transmission of the IL-18/ -607 C/A polymorphism to affected children. There is no correlation between the IgE level and the IL-18 -607 C/A promoter polymorphism. Our data indicate that IL-18 -607 C/A promoter polymorphism is associated with susceptibility to developing asthma in Tunisian population.