Background and objectives: The mechanisms leading to low effectiveness of the humoral immune response against P. aeruginosa in cystic fibrosis (CF) are poorly understood. The aim of the present study was to assess the avidity maturation of specific antipseudomonal IgG before and during the development of chronic lung infection in a cohort of Danish CF patients. Methods: Avidity maturation was assessed against a pooled P. aeruginosa antigen (St-Ag) and against P. aeruginosa alginate in 10 CF patients who developed chronic lung infection and 10 patients who developed intermittent lung colonization, using an ELISA technique with the thiocyanate elution method. Avidity was quantitatively determined by calculating the avidity Constant (Kav). Results: IgG avidity to St-Ag significantly increased at the onset (Median Kav = 2.47) and one year after the onset of chronic infection (Median Kav = 3.27), but did not significantly changed in patients who developed intermittent colonization. IgG avidity against alginate did not significantly change over the years neither in patients who developed chronic lung infection (Median Kav = 3.84 at the onset of chronic infection), nor in patients who developed intermittent colonization. Conclusion: IgG avidity to P. aeruginosa alginate does not significantly enhance as chronic lung infection progresses. This probably plays a role in the difficulty to mount an effective opsonophagocytic killing to clear mucoid P. aeruginosa infection in CF.