Serum IgG antibodies to Pseudomonas aeruginosa surface antigens were measured by enzyme linked immunosorbent assay in all patients with cystic fibrosis from whom P. aeruginosa was isolated for the first time during a study period of 18 months. In 15 patients the titre of serum IgG antibodies was greater than control values before or at the time of the first bacteriological isolation of P. aeruginosa. The presence of serum antibodies specific to P. aeruginosa suggests exposure to infection by that organism for some months before its isolation in significant numbers from the respiratory tract. In the other two patients serum titres were within the control range before isolation of P. aeruginosa but had increased to above the control range within the next month. Longitudinal studies on the entire group of patients showed further increases in titre concurrently with further isolations of P. aeruginosa. These results suggest that this assay may be an indicator of the beginning of pulmonary infection by P. aeruginosa and may prove to be a sensitive monitor of the progress of infection, and response to treatment, during the first months of infection by that organism.