Histamine (H2)-receptor blockers are commonly used in critically ill patients to prevent gastric bleeding and have been implicated in the pathogenesis of gram-negative bacterial (GNB) nosocomial pneumonia. These experiments were undertaken to determine if cimetidine affects pulmonary GNB clearance. Groups of normal Sprague-Dawley rats were given cimetidine (75 mg/kg) or an equal volume of sterile buffer intraperitoneally every 6 hr for 24 hr prior to intratracheal challenge with 1.0 x 10(8) Pseudomonas aeruginosa. At 6 and 24 hr after challenge, animals were sacrificed and gastric pH, quantitative lung cultures, and total and differential [alveolar macrophages (AM) and polymorphonuclear leukocytes (PMN)] cell counts in bronchoalveolar lavage fluid were performed. Results showed that cimetidine therapy resulting in gastric pH greater than 4.0 has no effect on the pulmonary clearance of P. aeruginosa.