Using an in vitro model, we compared efficiencies of jet nebulizers and metered-dose inhalers (MDI) with actuator devices to deliver albuterol in various conditions of mechanical ventilation. Factors tested included influence of humidification, MDI actuator device (Aerovent spacer or Marquest 172275 MDI adaptor), and synchronization of MDI to the respiratory cycle. With the nebulizer (AeroTech II) filled with 2.5 mg albuterol sulfate in 3 ml water and run until dry, inhaled mass was 42 +/- 2.6% and mass median aerodynamic diameter (MMAD) was 1.3 microns on a nonhumidified circuit. With the MDI+ Aerovent, the inhaled mass percentage per 90 microgm puff was 15.4 +/- 0.2% with humidification and 25.1 +/- 3.7% without humidification, actuations being synchronized with the beginning of inspiration and separated by a 1-min pause. Failure to synchronize actuations with inspiration or to pause 1 min resulted in significant reductions in inhaled mass (by 35 and 72%, respectively). The Marquest adaptor was less efficient, with an inhaled mass of 7.2 +/- 0.7% under optimal conditions. Metered-dose inhaler actuation during expiration resulted in relatively large particles (MMAD = 2.0 microns). All other MDI actuations led to essentially biphasic distributions, with particles greater than 1 micron following a distribution similar to the nebulizer and the overall MMAD estimated to be 0.22 microns. The AeroTech II delivered a cumulative 1,000 micrograms of drug (2,500 x 0.40) over 40 min. To achieve that amount, the MDI connected to the Aerovent and used in its most efficient sequence would require 45 timed puffs (90 micrograms per puff, 25.1% mean inhaled mass) and take 45 min of an experienced therapist's time.(ABSTRACT TRUNCATED AT 250 WORDS)