The incidence of nosocomial pneumonia in long-term ventilated patients has been reduced by stress ulcer prophylaxis with sucralfate. In a double-blind trial we studied whether gentamicin administered topically to the oropharynx (OPG) had additional clinical benefits in these patients. 67 critically ill adult patients fulfilled entry criteria for > or = 5 days on ventilation. The OPG group received 40 mg gentamicin, the control group received 5% dextrose topically administered to the oropharynx 4 times a day. During OPG, pharyngeal colonization rate (21 vs 44%) and tracheal secretion colonization rate (12 vs 41%) were significantly lower than during placebo (p < 0.05). Despite these differences nosocomial pneumonia rate (3 vs 12%), duration of mechanical ventilation [15.8 +/- 11.1 vs 19.9 +/- 37.5 days (means +/- SD)] and mortality (27 vs 41%) were not significantly affected by OPG. Moreover, 13 of 15 bacteria (87%) that occurred during OPG were resistant to gentamicin. Despite its reduction of bacterial colonization rates of pharyngeal and tracheal secretions, OPG did not seem to offer additional clinical benefits in long-term mechanically ventilated patients on stress ulcer prophylaxis with sucralfate.