The mechanical work of breathing (WOB), can be determined from the simultaneous measurement of changes in volume displacement and pressure (WOB=ΔV·ΔP). We designed a lung simulator device which typifies a breathing, intubated neonate in compliance, frequency, inspiratory flowrate, resistance and tidal volume (2cc/cmH2O, 50/minute, 80cc/second, 3.0 ET tube, 10cc respectively). All measurements were at the airway opening via a calibrated transducer/recorder system with a frequency response flat to >50 Hz.We evaluated the performance of the BABYbird 1R, BABYbird 2R Bear BP-200R, Bear-2001 ‘Cub’R, Healthdyne 105R, Healthdyne 200R and Sechrist IV-100BR. All units were stock and represented a wide sampling of current continuos flow, pressure limited, time cycled neonatal ventilators. Excluding the exhalation valve, the ventilator circuits were identical (TYGONR tubing, 0.3cc/cmH2O, compliance). The following settings were used during the test period: inspiratory time= 1.0 second, peak inspiratory pressure= 25 cmH2O, and PEEP= 5 cmH2O.Mechanical WOB ranged from 140 to 240 cc·cmH2O during the IMV breaths and 110 to 200 in the PEEP interval. The Healthdyne 105R had the lowest WOB in both periods whereas the greatest WOB occurred with the Sechrist in IMV and Bear Cub in PEEP. We have used clinically all of the ventilators tested and have not noted any deleterious results secondary to the diversity in mechanical WOB. However, the WOB difference is broad and may have subtle and/or patient compensated effects on the spontaneously breathing infant being exposed to mechanical ventilation.