In a three-way crossover pilot study, the acute effects of tiotropium 18 microg inhalation on the respiratory function and arterial blood gas tensions of 30 patients with stable chronic obstructive pulmonary disease (COPD) were compared with those of salmeterol 50 microg and formoterol 12 microg. In each study day, lung function and arterial blood gas analyses were performed before and up to 180 min after inhalation. All treatments significantly improved lung function, increased DLco, decreased PaO2, and increased P(A-a)O2, with no change in PaCO2. The effects of salmeterol and tiotropium on PaO2 were slower in onset and more prolonged than those of formoterol but PaO2AUC0-180 min was significantly greater for formoterol and salmeterol than for tiotropium. It is likely that the significant but small decreases in PaO2 and increases in P(A-a)O2 have been caused by pulmonary vasodilator effects. Since the three agents were similar in inducing bronchodilation, we believe that tiotropium is preferable in patients with hypoxemia caused by stable COPD because it seems to carry a smaller risk of worsening systemic hypoxemia.