Pseudomonas aeruginosa infection of the respiratory tract in patients with cystic fibrosis is a major determinant of morbidity and mortality. However, it has been postulated that the earliest phase of colonization is not associated with injury. To test this hypothesis we determined the association of the first recorded isolation of P. aeruginosa from the sputum on circulating markers of the inflammatory response in 6 patients with cystic fibrosis. At this time circulating C-reactive protein was increased in all 6 and neutrophil elastase alpha 1-antitrypsin complex (elastase-complex) was increased in 5 patients compared with healthy controls. This inflammatory response was associated with a reduction in the FEV1 and FVC of all patients [FEV1, 1.42 +/- 0.87 L (mean +/- SD) at first isolation vs. 2.08 +/- 0.74 L before isolation; P < 0.05; FVC, 1.94 +/- 0.93 L vs. 2.87 +/- 1.01 L, P < 0.05]. At a median interval of 10 months, 5 patients had raised titres of positive IgG antibody to P. aeruginosa, indicating significant exposure to this organism. At this time, lung function had returned to preinfection levels, whilst 3 patients showed continuing features of an inflammatory response, and the group mean value for elastase-complex was raised. Our findings demonstrate that at the time of first isolation of P. aeruginosa from the sputum of patients with cystic fibrosis, there is a concomitant systemic host response and an acute deterioration of pulmonary function.