Several studies have suggested that anticholinergics are at least equal to or may be superior to beta agonists in the treatment of stable COPD. However, since most previous studies have been performed to evaluate the bronchodilating effects of these two agents at relatively high doses, the clinical value of combining these two agents still is under debate. The purpose of this study was to determine if combination therapy with ipratropium bromide and salbutamol, in clinically available dosages, is superior in bronchodilation to ipratropium bromide alone. Twenty-six male patients (mean age, 67.5 +/- 5.9 years; FEV1, 0.87 +/- 0.32 L) with stable COPD were studied in randomized, double-blind, placebo-controlled experiments. On five separate days, all the patients received one of the following: (1) 40 micrograms ipratropium bromide, (2) 80 micrograms ipratropium bromide, (3) 40 micrograms ipratropium bromide plus 200 micrograms salbutamol, (4) 80 micrograms ipratropium bromide plus 400 micrograms salbutamol, or (5) placebo, using metered-dose inhalers (MDIs). Spirometry was assessed before and 15, 30, 60, 90, and 120 min after inhalation. Positive FEV1 responses to combined dosages of 80 micrograms ipratropium bromide and 400 micrograms salbutamol were significantly greater than responses to any other treatment regimen. Significantly greater responses also were achieved by combining 200 micrograms salbutamol with 40 micrograms ipratropium bromide compared with 40 micrograms ipratropium bromide alone. Combination therapy with 200 micrograms salbutamol and 40 micrograms ipratropium bromide produced a significantly greater effect on forced vital capacity than therapy with 80 micrograms ipratropium bromide alone. No significant differences were found between the responses induced by therapy with 80 and 40 micrograms ipratropium bromide. No adverse reactions to any regimen were noted throughout the study. In conclusion, combining the standard dosages of ipratropium bromide and salbutamol may provide greater bronchodilation than doubling the standard dosage of ipratropium bromide in patients with COPD.