Inflammation and mucosal immune system activation have an important role in irritable bowel syndrome (IBS), whereas genetic factors can control some immunological mediators. In this study, a number of polymorphic genes coding for T-helper 1, T-helper 2, and T-regulatory cytokines were genotyped in 71 patients with IBS, and the results were compared with controls. IL-4 CC genotype at position -590, IL-4 TT genotype at position -33, and IL-10 GA genotype at position -1082 were significantly overrepresented in the patients with IBS in comparison with controls (P < 0.001). The frequencies of the following haplotypes in the patient group were significantly higher than in the control group: IL-2 (-330, +160) GT haplotype (P = 0.002), IL-4 (-1098, -590, -33) TCC haplotype (P < 0.001), and TCT haplotype (P < 0.001). While production of cytokines could be affected by genetic polymorphisms within coding and promoter regions of cytokine genes, IL-4 and IL-10 gene polymorphisms could affect individual susceptibility to IBS.