Sudden infant death syndrome (SIDS) is a major cause of infant death of unknown etiology. We propose that SIDS results from a genetically determined imbalance in the production of inflammatory and anti-inflammatory cytokines in response to the infant's microbial flora. We were especially interested to know the relationship between SIDS and genetically determined higher or lower production of IL-10, an anti-inflammatory cytokine. Biallelic polymorphisms in the promoter region of the IL-10 gene associated with higher or lower production of IL-10 were determined in a SIDS and in a control group using a sequence-specific oligonucleotide approach. One particular allele of the IL-10 gene, the IL-10-592*A allele, was significantly associated with SIDS. Indeed, 70% of the SIDS babies carried the IL-10-592*A allele (p = 0.007 compared with control). In addition, there was a significant reduction in the frequency of homozygosity for the allele IL-10-592*C (p = 0.001 compared with control). Carrying the A allele (either A/A or A/C) had an odds ratio of 3.3 (95% confidence interval 1.4-8.0). In the same patients there was no association with other IL-10 gene polymorphisms nor with other cytokine (TNF-alpha, TGF-beta 1) genotypes, emphasizing the particular relationship between SIDS and the IL-10-592*A allele.