Previous studies have suggested that nebulizers are inefficient in delivering aerosolized medication to the lung in patients supported by mechanical ventilation. In a recent bench study, we characterized factors that may affect aerosol delivery, i.e., nebulizer type, ventilator settings (duty cycle), volume fill, and humidification as well as technical factors affecting measurement of deposition (e.g., radiolabeled compounds). Utilizing the predictions from our bench data, the present study was designed to assess nebulized aerosol delivery to ventilated patients under optimal conditions. Seven patients who were receiving mechanical ventilation (Bear II) via tracheostomy tube (TT) were studied. The humidifier was turned off. The test aerosol, a saline solution labeled with 99mTechnetium bound to human serum albumin (99mTc-HSA), was administered via a jet nebulizer (AeroTech II, 1.1 +/- 1.8 microns [mass median aerodynamic diameter, MMAD, geometric standard deviation, sigma g]), which was incorporated into the ventilator circuit and run to dryness. Inhaled and deposited radioactivity were measured by a mass balance/filter technique. TT versus lung deposition were quantified by removal of the inner cannula and direct measurement of TT deposition in a well counter. Inspiratory versus expiratory components of TT deposition were separated via bench techniques for each TT tube and breathing pattern. The regional distribution of deposited radioactivity was confirmed by gamma camera scans before and after TT removal. Measured radioactivity at each site was expressed as a percentage of nebulizer charge (i.e., the quantity of radioactivity originally placed in the nebulizer). On average, 30.6 +/- 6.3% (SD) of the charge was inhaled by the ventilated patients. Mean deposition in the TT during inspiration was 2.6 +/- 0.5%.(ABSTRACT TRUNCATED AT 250 WORDS)