Objective: To study the pulmonary effects of aspirating a mixture of sucralfate in water and sucralfate in hydrochloric acid in an animal model of aspiration pneumonia. Design: Prospective, randomized, controlled study with repeated measures. Setting: University research laboratory. Subjects: Thirty-two in situ, isolated, blood perfused porcine lung preparations. Interventions: Five control preparations received no aspiration. Twenty-seven preparations received a standard aspiration of 1.5 mL/kg body of a) distilled water (n = 5), b) sucralfate in distilled water (n = 8), c) 1/10 normal hydrochloric acid (n = 6), and d) mixture of sucralfate in distilled water and hydrochloric acid (n = 8). Measurements: The pH measurements were made of all aspirates. Lung weight, airway pressures, and pulmonary artery pressures were continuously monitored before and for 4 hrs after aspiration. Lung wet/dry weight ratio was measured at the completion of the study. Results: The pH of sucralfate mixed with distilled water was 4.9, pH of 1/10 normal hydrochloric acid was 1.0, and pH of equal volumes of a sucralfate-water suspension mixed with hydrochloric acid was 1.5. Airway pressures and pulmonary arterial pressures increased in all aspirate groups over time compared with those values of control lungs. Control lungs gained 18 +/- 3 (SEM) g over 4 hrs and the wet/dry ratio was 4.951 +/- 0.310. Lungs aspirating distilled water gained 147 +/- 49 g and the wet/dry ratio was 5.198 +/- 0.120. Lungs aspirating sucralfate and distilled water increased their weight by 109 +/- 30 g and the wet/dry ratio was 5.380 +/- 0.076. Lungs aspirating a suspension of sucralfate and water and hydrochloric acid were similar to lungs aspirating hydrochloric acid alone with weight increases of 265 +/- 30 g and 346 +/- 81 g, and the wet/dry ratio of 7.011 +/- 0.273 and 7.230 +/- 0.390, respectively. Conclusions: Sucralfate has minimal acid buffering effect. Aspiration of sucralfate mixed with distilled water causes lung edema similar to aspiration of water alone. Aspiration of a sucralfate-water suspension mixed with hydrochloric acid causes severe lung edema. These results suggest that patients given sucralfate prophylaxis for stress ulceration are at risk for acid aspiration.