Higher doses of inhaled albuterol have been shown to cause slightly more bronchodilatation than standard doses from a metered-dose inhaler in patients with severe chronic airflow limitation. Higher doses, however, carry an increased risk of side effects, and the optimum dose balancing benefit and adverse effects have yet to be established. We have therefore looked at objective and subjective evidence of beneficial and adverse effects after 4 doses of albuterol in 30 patients with chronic bronchitis, severe airflow limitation, and less than 200 ml increase in FEV1 after 200 micrograms inhaled albuterol. Subjects were given placebo, 400 micrograms, 1 mg, 2 mg, and 4 mg albuterol by dry powder inhaler in random order on separate days in a double-blind study, and FEV1, relaxed VC, PEFR, 12-min walk distance, finger tremor, oxygen saturation, heart rate, and arrhythmias were measured at intervals over 6 h. With increasing doses of albuterol, there was a significant dose-related increase in FEV1, VC, and PEFR, the maximal mean changes being 196 ml, 480 ml, and 50 L/min, respectively. The duration of effect was longer with the higher doses. There was a dose-related increase in heart rate, tremor amplitude, and supraventricular ectopic beats and a dose-related fall in oxygen saturation. There was no drug-related effect on the frequency of ventricular ectopic beats either at rest or during the walk tests. The largest increases in walk distance occurred after the 1 and 2 mg doses and the least after the 4 mg dose.(ABSTRACT TRUNCATED AT 250 WORDS)