Polymorphonuclear leukocytes (PMNL) or Pseudomonas aeruginosa can damage the lung, but the manner in which they interact to induce toxicity is unclear. An in vitro model of the pulmonary epithelium was used to investigate interactions of PMNL and P. aeruginosa on epithelial cytotoxicity. A low inoculum of P. aeruginosa (10(7) bacteria) was minimally toxic to the epithelial cells (lysis = 9.0 +/- 2.9, detachment = 3.5 +/- 1.4). The addition of PMNL to the low inoculum markedly increased damage to the epithelial cells (lysis = 18.1 +/- 3.9, detachment = 17.6 +/- 3.6). Both the bacterium and a low-molecular-weight exoproduct were able to induce PMNL-mediated damage to epithelial cells. The damage was inhibited by serum or the addition of alpha 1 antiprotease but not by antioxidants. A larger inoculum of P. aeruginosa (10(9) bacteria) was directly toxic to the pulmonary cells (lysis = 44.8 +/- 4.1, detachment = 7.6 +/- 0.7). The damage was mediated by a heat-labile bacterial exoproduct. Pulmonary epithelial damage following pseudomonal infections may be related to either neutrophil or bacterial activity depending on the bacterial inoculum.