There is controversy whether routine use of theophylline is warranted in chronic obstructive pulmonary disease (COPD). Effects on spirometry are minimal, and subjective relief is difficult to document. Therefore, we undertook to study the pulmonary effects of theophyline using a functional approach, namely, its effects on the lung mechanics of a standing or walking patient. In a double blind, placebo controlled crossover study, 400 mg of slow-release theophylline (TheoDur) were given twice a day in 13 trials to 10 patients with severe COPD. Lung mechanics were calculated on a breath-by-breath basis by a pulmonary mechanics computer from esophageal pressures and flow. Expired volumes were simultaneously collected. Spirometry was then performed. On the placebo limb, the spirometric response to 0.5 mg terbutaline given subcutaneously was compared with the theophylline response. At a mean serum theophylline level of 12.3 micrograms/ml, theophylline produced in the entire group a mean reduction in the work of breathing done on the lung (WL) of 16% (p less than 0.002) while walking, but a significant effect while standing was not detected. During both walking and standing, the mean reduction in lung resistance (RL) was 15 to 16% (p less than 0.002). Minute volume (VE) was increased at borderline significance, with a mean reduction while walking of 19% in the ratio of WL to VE (p less than 0.002). In the individual patient, changes in WL were influenced more by changes in VE than by changes in RL; in fact, changes in WL correlated best with changes in the product of (VE)2 and RL. Theophylline produced a mean increase of 15% in forced expiratory volume in one second (FEV1) and 16% in forced vital capacity (FVC).(ABSTRACT TRUNCATED AT 250 WORDS)