Several factors may affect the delivery of a nebulized aerosol to the lung through an endotracheal tube during mechanical ventilation. To study these factors in vitro, a model representing ventilation of an adult patient was constructed by linking a Servo 900C ventilator to a standard humidified circuit and an endotracheal (ET) tube positioned within a pipe representing the trachea. This was connected via a filter to a lung simulator. Nebulizers filled with 99mTc human serum albumin were positioned in the circuit, and the delivery of nebulized aerosol through the ET tube into the filter was measured using a gamma camera. With the use of an inspiratory phase-activated System 22 Acorn jet nebulizer, typical adult ventilator settings, and a 3-ml nebulizer solution volume, 5.4% of the nebulizer dose reached beyond the end of the ET tube. This was increased by increasing the inspiratory time, reducing the respiratory rate or respiratory minute volume, and by repositioning the nebulizer on the inspiratory limb of the Y-piece and was reduced by slowing the driving gas flow to the nebulizer. Under the same conditions, delivery was 3.1 and 4.4% using the Samsonic and Fisoneb ultrasonic nebulizers, respectively. Increasing the fill volume and the addition of an aerosol storage chamber increased delivery with all three nebulizers. These experiments suggest some simple ways of improving aerosol delivery during mechanical ventilation, including increasing the volume of nebulizer fill, repositioning the nebulizer in the ventilator circuit, adding an aerosol storage chamber, and adjusting ventilator settings to maximize delivery.