The effect of a large tracheal tube cuff on the rabbit tracheal mucosa was investigated by phase contrast microscopy and scanning (SEM) and transmission (TEM) electron microscopy. The tube was left in the trachea for 15 min. The cuff was either uninflated or inflated to a cuff-to-tracheal wall pressure (C-T pressure) of up to 100 mmHg. The uninflated cuff caused superficial damage to the epithelial lamina over regions where a cartilage was situated. When the cuff was inflated, it resulted in an increase of the mucosal damage, the extent of which was directly related to the pressure in the cuff. This took the form of both widening of the injured areas and penetration of the damage to deeper regions. At a C-T pressure of 100 mmHg the damage involved almost the entire mucosa and only small unaffected mucosal regions remained. At this stage it appeared as if the basement membrane had also begun to disintegrate. It is well known that a small cuff easily causes deep ulceration in the mucosa overlying the cartilages. From this investigation it was concluded that a large cuff causes the same type of ulceration if 1) the cuff wall is not sufficiently thin and pliable, and 2) if the cuff is overinflated enough to dilate the trachea to a diameter exceeding the cuff-diameter. At that moment there will be circumferential tension in the cuff and the sealing physics of the large cuff will become the sealing physics of a small (high pressure) cuff. A large cuff, properly handled, is more benign to the trachea than a small cuff. In order to avoid overinflation of the large cuff, the intracuff pressure (= C-T pressure) should always be measured by means of a four-way stopcock and an aneroid manometer. In the case of extended periods of mechanical ventilation with a high airway pressure, the resulting tracheal diameter at the cuff site should be checked radiographically.