In the UK, Sudden Infant Death Syndrome (SIDS) is a major cause of postperinatal mortality up to the end of the first year of life. Several studies have found an association between cytokine IL-10 genotypes and SIDS. The aim of the present work was to test the hypothesis that SIDS is associated with high producer gene polymorphisms for certain proinflammatory cytokines and with low producer gene polymorphisms of certain antiinflammatory cytokines. DNA polymorphisms were investigated using sequence-specific primer (SSP)-polymerase chain reaction (PCR). Results demonstrated that SIDS and controls did not differ significantly with respect to genotype distributions for IL-4 -590 (chi(2) test, p = 0.164), IFN- gamma +874 (p = 0.050), or TGF-beta1 +869 (p = 0.322). However, significant associations with SIDS were seen for genotypes of VEGF -1154 (p = 0.005) and IL-6 -174 (p = 0.018). Comparison of allele frequencies for these cytokine genes between SIDS and control groups reflected the genotype data. Allele frequencies that did not demonstrate significant differences between test groups were IL-4 -590*T (chi2, p = 0.104), IFN- gamma +874*A (p = 0.052), and TGF-beta1 +869*C (p = 0.468). Those demonstrating significant differences between SIDS and control groups were VEGF -1154*A (p= 0.002, OR = 2.94, CI 1.46-6.02) and IL-6 -174*G (p= 0.034, OR = 2.18 CI 1.05-4.56). Thus, there are associations between SIDS and particular polymorphisms of VEGF and IL-6 cytokine genes in addition to those previously found in Manchester with another cohort of samples for the antiinflammatory cytokine IL-10. Moreover, these gene polymorphism associations suggest that the causation of SIDS is related to both fetal lung development and a child's innate ability to mount an inflammatory response to infection.