Histological and ultrastructural changes in the nasal mucosa of normal and leukopenic mice exposed to Pseudomonas aeruginosa were compared and correlated with changes in the distribution of pseudomonads by use of immunoperoxidase labeling. Pseudomonas was limited to the surface of the nasal mucosa of normal mice and was cleared rapidly. Concurrently, granulocytes were recruited across unaltered nasal epithelium and contained phagocytosed bacilli within two hours. Pseudomonas was limited to the surface of the nasal mucosa of most leukopenic mice at two hours. By four hours, pseudomonads had penetrated interepithelial junctions of all leukopenic mice. Granulocytes were not recruited and nasal epithelium underwent necrosis at points of invasion. These results show that neutrophils participate in the clearance of P. aeruginosa from the surface of the nasal mucosa and that the failure to recruit granulocytes may be important in the breakdown of epithelial barriers. Possible mechanisms of mucosal invasion are discussed.