A role of immunological factors in glioma etiology is suggested by reports of an inverse relationship with history of allergy or autoimmune disease. To test whether single-nucleotide polymorphisms (SNPs) in cytokine genes were related to risk of adult glioma, we genotyped 11 SNPs in seven cytokine genes within a hospital-based study conducted by the National Cancer Institute and an independent, population-based study by the National Institute for Occupational Safety and Health (overall 756 cases and 1190 controls with blood samples). The IL4 (rs2243248, -1098T>G) and IL6 (rs1800795, -174G>C) polymorphisms were significantly associated with risk of glioma in the pooled analysis (P trend = 0.006 and 0.04, respectively), although these became attenuated after controlling for the false discovery rate (P trend = 0.07 and 0.22, respectively). Our results underscore the importance of pooled analyses in genetic association studies and suggest that SNPs in cytokine genes may influence susceptibility to glioma.