The chronic Pseudomonas aeruginosa lung infection in cystic fibrosis (CF) is characterized by a pronounced antibody response and microcolonies surrounded by numerous polymorphonuclear neutrophils (PMN). Poor prognosis is correlated with a high antibody response to P. aeruginosa antigens. An animal model of this infection was established in two strains of mice: C3H/HeN and BALB/c, generally known as Th1 and Th2 responders, respectively, which were challenged with alginate-embedded P. aeruginosa. Mortality was significantly lower in C3H/HeN compared to BALB/c mice (p <0.025). P. aeruginosa was cleared more efficiently in C3H/HeN mice and significantly more C3H/HeN mice showed normal lung histopathology (p <0.02), and we found significantly fewer microabscesses in C3H/HeN mice than in BALB/c mice (p <0.005). In supernatants from P. aeruginosa antigen and concanavalin A-stimulated spleen cells from the two strains of mice, the interferon-(IFN-) gamma levels were higher, whereas IL-4 levels were lower in C3H/HeN mice than in BALB/c mice. The implications of these findings for CF patients with chronic P. aeruginosa lung infection are discussed.