C-reactive protein (CRP) is a general marker of the systemic inflammatory response to bacterial infection. Serial measurement of CRP is useful in monitoring respiratory exacerbations in patients with cystic fibrosis (CF) and chronic infection with Pseudomonas aeruginosa. We hypothesized that regular monitoring of CRP in young children with CF prior to colonization with P. aeruginosa might provide an objective guide to the need for antibiotic treatment. Twenty-two children were studied prospectively over a 6 month period. We measured CRP every 2 months and at the beginning and end of respiratory exacerbations. In samples taken when the children were well, median CRP was 0.45 microgram/mL compared with 1.92 micrograms/mL when they were symptomatic with positive culture results (P < 0.05). Despite this difference there was considerable overlap between CRP levels for infected and noninfected patients. A CRP value of > 1.82 micrograms/mL (the upper 95% confidence interval for a control group of well children without CF) had a sensitivity of 49% and a specificity of 83% in determining a symptomatic exacerbation. We conclude that in this group of patients CRP measurements were of little value in monitoring respiratory exacerbations in patients who become intermittently infected with either Haemophilus influenzae or Staphylococcus aureus.