Retrograde colonization of the oropharynx from the stomach by microaspiration of gastric fluid is a recently recognized phenomenon associated with increased gastric pH that may result in pneumonia during ventilation therapy. In a prospective study we investigated 104 mechanically ventilated patients in the intensive care unit who were receiving sucralfate (n = 49) or cimetidine (n = 55) for stress ulcer prophylaxis. The incidence of pneumonia was 45.5% (25 patients) in the cimetidine group and 26.5% (13 patients) in the sucralfate group (95% confidence interval 0.98 to 6.97; odds ratio 2.61; p = 0.0549). Mortality rates were 18.4% (9 patients) in the sucralfate group versus 25.5% (14 patients) in the cimetidine group (p = 0.48). The mean pH values of gastric aspirates were significantly lower in patients treated with sucralfate than in patients receiving cimetidine (p = 0.044). The number of colony-forming units of Enterobacteriaceae in gastric aspirates was also significantly lower in the sucralfate group (p = 0.0037).