Objective. The inflammatory bowel diseases (IBDs), including Crohn's disease ( CD) and ulcerative colitis (UC), are multifactorial diseases resulting from a complex interaction of genetic and environmental factors. The recently described CARD15 and TNF-alpha risk alleles are believed to be contributors to disease by disrupting inflammatory pathways via impaired response to bacteria. Other bacterial receptors, such as CD14, may also have a role in disease. A promoter polymorphism ( - 159C/T) in CD14 has been implicated in IBD in a number of studies. Material and methods. We have analysed this CD14 promoter polymorphism in probands from 206 multiplex IBD families, 110 sporadic IBD individuals and 189 healthy controls from the Australian population, all of whom are Caucasian. Results. We could not replicate the described association between the CD14-159T allele and CD or UC, nor did we find any evidence for an interaction between the CARD15 or TNF-alpha risk alleles and the CD14-159T allele. Conclusions. It is possible that the association seen in other studies may be due to population stratification or to the CD14 polymorphism being in linkage with the real disease-causing variant(s).