In nonintubated patients, beta 2-agonist bronchodilators are equally effective when delivered by metered-dose inhalers (MDI) or nebulizers (NEB). The delivery of these drugs by MDI to intubated, mechanically ventilated patients has become a widespread practice. To compare the efficacy of the two delivery systems and establish optimal dosing, we prospectively randomized 10 mechanically ventilated patients, with increased airways resistance, to receive albuterol by either MDI or nebulizer in incrementally higher doses. After a 4-hr washout, patients were crossed-over to receive the drug by the alternative route of administration. Albuterol delivered by NEB to a total dose of 2.5 mg reduced the inspiratory flow-resistive pressure (peak-pause airway pressures) from 21.5 +/- 5.7 to 17.6 +/- 5.4 cm H2O (p < 0.01). Nebulized albuterol at cumulative doses of 7.5 mg led to further reductions in 8 of 10 patients (p < 0.1), but led to toxic side effects in 4 of them; in the remaining 6 patients toxicity occurred at a cumulative dose of 15.0 mg. By contrast, albuterol in cumulative doses reaching 100 puffs (9 mg) from an MDI administered into an endotracheal tube adapter did not significantly reduce resistive pressures, and produced no toxicity. We conclude that nebulized albuterol provides objective physiologic improvement, while albuterol administered by MDI through an endotracheal tube adapter has no effect in mechanically ventilated patients with airflow obstruction. Nebulizer treatments can and should be titrated to higher-than-conventional doses, using toxic side-effects and physiologic response to guide therapy.