Anti-cholinergic agents are generally regarded as the bronchodilator therapy of first choice in the treatment of stable chronic obstructive pulmonary disease (COPD), considering that they may be more effective than in inhaled beta 2-agonist. However, results of the authors' recent studies conflict to some extent with this suggestion because they demonstrate that this is true only for short acting beta 2-agonists but not for long-acting beta 2-agonists. Oxitropium bromide is an anti-cholinergic drug that has been shown to produce a similar degree of bronchodilation to that obtained with ipratropium bromide, but with a longer-lasting effect. In the present study, the time course of inhaled oxitropium bromide bronchodilation in comparison to that of inhaled salmeterol in a group of patients with partially reversible COPD was evaluated. Twelve male patients with moderate to severe COPD participated in the study. The study had a single-bind, cross-over, randomized design. The bronchodilator activity of 50 micrograms salmeterol hydroxynaphthoate, 200 and 400 micrograms oxitropium bromide and placebo, which were all inhaled from a metered-dose inhaler, was investigated on several non-consecutive days. The highest FVC and FEV1, obtained from one or the other of the reproducible curves, were kept for analysis. Measurements were performed at the following times: immediately before inhalation of treatment, and at 15, 30, 60, 120, 180, 240, 300, 360, 480, 600 and 720 min after inhalation of the individual treatment. Salmeterol tended to have a delayed time to peak effect, but had a longer duration of effect than oxitropium. The response to salmeterol exceeded the response to 200 micrograms oxitropium for 12 h, but its responses were significantly (P < 0.05) greater than those to 200 micrograms oxitropium from 10 to 12 h. From 3 to 12 h, salmeterol also surpassed 400 micrograms oxitropium but differences were not significant (P < 0.05). The mean FEV1 area under the curve was significantly (P < 0.05) larger after salmeterol when compared to 200 micrograms oxitropium bromide, but there was no significant difference (P < 0.05) between salmeterol and 400 micrograms oxitropium bromide. No significant changes in pulse rate, blood pressure or electrocardiograms were found among the four groups as compared with placebo group. These findings confirm and extend what has been demonstrated by the authors' previous studies, and show that salmeterol compares conveniently with anti-cholinergic drugs in terms of effects on lung function at clinically recommended doses.