We have previously demonstrated that lower esophageal sphincter (LES) dysfunction is induced in healthy volunteers placed in negative pressure body ventilators. This is important, because regurgitation of gastric contents and peptic esophagitis are frequent complications of the use of such ventilators. The present study was conducted to determine whether LES dysfunction during the use of these ventilators also occurs in patients with chronic respiratory failure, and whether this dysfunction can be pharmacologically reversed. Seven patients with documented chronic respiratory failure due to COPD were studied. After an overnight fast, esophageal, LES, and gastric pressures were simultaneously recorded in the unassisted state and during mechanically assisted ventilation, after which 10 mg iv metoclopramide were administered to each patient, and pressure recordings were continued for 1 h more. In all seven patients, baseline LES pressures were in the normal range. During the inspiratory cycle of mechanical ventilation, five of the seven patients demonstrated a significant reduction in LES pressure, whereas it was unchanged in the other two. Within 15 min of metoclopramide administration, there was an increase in LES pressure to baseline levels in the five patients in which a significant decrease in LES pressure had occurred. Metoclopramide did not have any effect on the LES pressure of the other two patients. Thus, we conclude that in patients with chronic respiratory failure, as in normals, there is a subset of individuals in whom negative pressure mechanical ventilatory assistance induces dysfunction of the LES, and that this dysfunction is reversible with metoclopramide.