BACKGROUND: Nasal CPAP is widely used in neonatal ICUs. Aerosolized medications such as inhaled steroids and ␤ agonists are commonly administered in-line through nasal CPAP, especially to infants with bronchopulmonary dysplasia. We hypothesized that aerosol delivery to the lungs via variable-flow nasal CPAP in an in vitro model would be unreliable, and that the delivery would depend on the position of the aerosol generator within the nasal CPAP circuit. METHODS: We used a system that employed a test lung placed in a plastic jar and subjected to negative pressure. Simulated inspiration effort was measured with a heated-wire anemometer. We used technetium99m-labeled diethylene triamine penta-acetic acid as our aerosol. The nebulizer was placed either close to the humidifier or close to the nasal prongs in the circuit, and patient effort was simulated with a minute ventilation of 0.4 L/min. RESULTS: Relative aerosol delivery to the infant test lung with the nebulizer close to the humidifier was extremely low (0.3 ؎ 0.4%), whereas placing the nebulizer close to the nasal prongs resulted in significantly (P < .001) improved delivery (21 ؎ 11%). Major areas of aerosol deposition with the nebulizer close to the humidifier versus close to the nasal prongs were: nebulizer (10 ؎ 4% vs 33 ؎ 13%, P < .001), exhalation limb (9 ؎ 17% vs 26 ؎ 30%, P ‫؍‬ .23), and generator tubing (21 ؎ 11% vs 19 ؎ 20%, P ‫؍‬ .86). Placing the nebulizer close to the humidifier resulted in 59 ؎ 8% of the aerosol being deposited in the inhalation tubing along the heater wire. CONCLUSIONS: Isotope delivery from an aerosol generator placed near the humidifier on variable-flow nasal CPAP was negligible in this in vitro setup; however, such delivery was significantly improved by locating the aerosol generator closer to the nasal CPAP interface.