Similarities have been drawn between models of endotoxic shock and gross and microscopic pathology observed in sudden infant death syndrome (SIDS) cases. Polymorphisms in genes that influence the expression of endotoxin receptors could affect the outcome of toxaemia, and could, therefore, play a role in SIDS. The CD14 gene promoter contains a single nucleotide polymorphism that affects the level of CD14 gene expression. The TT genotype of the CD14 (C-260T) polymorphism causes a significantly higher density of CD14 receptor expression on monocytes which makes the individual more sensitive to endotoxin than those with the wild-type (CC). This investigation was designed to determine whether SIDS infants have a higher frequency of the CD14 (C-260T) polymorphism compared with non-SIDS controls. One hundred and sixteen SIDS and 228 control infants were genotyped using PCR followed by restriction fragment length analysis of amplified product. Carriage of the TT or CT genotypes did not significantly differ between SIDS and control infants (P = 0.218 and 0.081, respectively). The frequencies observed in the control group were consistent with Hardy-Weinberg equilibrium and did not differ significantly from the published frequencies in Caucasian Australians. These results suggest that CD14 (C-260T) polymorphism is unlikely to be implicated in SIDS.