Early acquisition of Pseudomonas aeruginosa is associated with a poorer prognosis in patients with cystic fibrosis. We investigated whether polymorphisms in CD14, the lipopolysaccharide receptor, increase the risk of early infection. Forty-five children with cystic fibrosis were investigated with annual bronchoalveolar lavage (BAL) and plasma sCD14 levels. Plasma sCD14 levels were significantly lower in children from whom P. aeruginosa was subsequently isolated (492.75 mu g/ml vs. 1339.43 mu g/ml, p = 0.018). Those with the CD14 - 159CC genotype had a significantly increased risk of early infection with P. aeruginosa suggesting that CD14 C-159T plays a role in determining the risk of early infection with P. aeruginosa.