We have compared a chronic lung infection with Pseudomonas aeruginosa embedded in alginate beads in normal and athymic rats with an acute infection with free live P. aeruginosa bacteria. The following parameters were observed and described: mortality, macroscopic and microscopic pathologic changes, and antibody responses. The rats challenged with P. aeruginosa alginate beads experienced a generally more severe lung pathology and the antibody responses were more homogeneous with less dispersion as compared to the rats having free live P. aeruginosa bacteria. In general, manifestations were more severe in the athymic rats compared to the normal rats. It is, however, notable that the athymic rats developed similar microscopic lung manifestations as the normal rats when given a large number of P. aeruginosa in the beads, with dense accumulation of neutrophil granulocytes and microcolonies comparable to the lesions seen in cystic fibrosis (CF) patients. Early transitory IgM titers were demonstrated in both normal and athymic rats. Whilst athymic rats produced much lower IgG titers than the normal rats, presumably due to the absence of CD4+ cells, higher primary IgA titers were achieved. These two models in normal and athymic rats of the chronic lung infection resembling that seen in CF lungs make it possible to study the influence of the various components of the specific and nonspecific defense systems on the course of the chronic P. aeruginosa lung infection and to evaluate the effect of various immunization schedules and immunomodulatory drugs.