Thirteen clinically stable male patients aged 63 +/- 3 years with irreversible airway disease were given aminophylline and placebo in a randomized crossover fashion on two consecutive days while receiving beta-agonists. During incremental exercise the maximal heart rate (139.0 +/- 22.1 vs 128.0 +/- 16.4 beats per minute) and minute ventilation (41.9 +/- 6.9 vs 38.1 +/- 8.2 L/min) were significantly higher and the arterial carbon dioxide pressure (34.6 +/- 5.0 vs 38.6 +/- 7.7 mm Hg) was significantly lower during aminophylline administration than during placebo administration. However, spirometric findings, maximal inspiratory pressures, maximal oxygen consumption, work rate, and arterial oxygen pressure were similar on both regimens. We concluded that the major effect of aminophylline is to increase ventilatory drive in patients with irreversible airway obstruction. Unless an objective change in spirometric data or exercise capacity can be documented, we believe that aminophylline therapy is not warranted in these patients.