We have shown previously that the administration of morphine (0.8 mg/kg) to patients with COPD increases the VO2max by 19.3 percent. A recent study demonstrated that the administration of low-dose nebulized morphine (approximately 2 mg) increased the endurance time of patients with severe lung disease by 1 min (35 percent) with few systemic side effects. This double-blind crossover study evaluated the effects of various doses of nebulized morphine (0, 1, 4, and 10 mg) on the exercise tolerance and the psychologic status of COPD patients. In the present study, eight COPD patients (FEV1 = 0.90 +/- 0.26 L, workload max = 76 +/- 29 W, VO2max = 950 +/- 264 ml, VEmax = 34 +/- 7 L), who were ventilatory limited were tested on four separate days. On each testing day, the patients underwent incremental exercise testing and psychologic testing before and 45 min after receiving the nebulized solution. The mean changes (+/- SD) in the exercise test results after each of the four different regimens were as follows: [table: see text] Although there tended to be larger increases in the workload, VO2max, and VEmax after the largest dose of morphine, none of the changes was statistically significant. Likewise, there were no significant differences in spirometry, resting metabolic measurements, or psychologic test scores after the four different regimens. We conclude that aerosolized morphine in the doses used in this study has no significant beneficial effect on the exercise tolerance of patients with COPD.