Systemic immunization with killed Pseudomonas improves pulmonary clearance of these bacteria in normal mice. To test the effects of active systemic immunization on early pulmonary clearance of Pseudomonas in neutropenic mice, Balb/c mice were intraperitoneally immunized with 10(8) Pseudomonas or injected with saline twice weekly for 2 wk. Ten days after the last immunization, immunized and control mice received tail vein injections with either nitrogen mustard or saline daily for 3 days. Two days after the last nitrogen mustard injection, mice were intrabronchially challenged with 10(6) or 10(4) live Pseudomonas and clearance was assessed 4 h later. With the higher inoculum, immunization (neutrophil-replete and neutropenic mice) augmented pulmonary clearance. The improvement in clearance with the higher inoculum was associated with a marked increase in bronchoalveolar lavage anti-Pseudomonas IgG. However, bacteria grew in the lungs of all neutropenic mice. Immunization did not alter pulmonary clearance of the lower inoculum of Pseudomonas, and bacterial growth occurred in the neutropenic mice. Gentamicin was administered to mice 2 h after intrabronchial challenge with 10(6) Pseudomonas to determine whether its effects were additive to immunization. Gentamicin improved pulmonary clearance effected by immunization only in the neutrophil-replete mice; immunization provided no additional benefit to gentamicin in the neutropenic mice. These data show that both neutrophils and immunization contribute to Pseudomonas clearance. Immunization improves pulmonary clearance of Pseudomonas in neutropenic mice with a sufficiently high inoculum, but bacterial growth still occurs. Gentamicin treatment is effective in eliminating bacteria in this model and immunization has no additional benefit.