To investigate the effect of intravenously administered aminophylline and 100% O2 breathing on ventilation-perfusion (VA/Q) inequality, nine patients recovering from an acute exacerbation of chronic obstructive pulmonary disease (COPD) were studied. The design was double-blind, crossover, placebo-controlled for aminophylline, and a single-blind, controlled protocol for O2, patients being studied on two successive days. Forced spirometry, systemic hemodynamics, arterial pH, and blood gases were measured together with the VA/Q distribution using the multiple inert gas elimination technique, and then a loading dose of aminophylline (6 mg/kg body weight) or placebo was given over 20 min followed by a maintenance infusion at 0.9 mg/kg/h that was kept constant for the rest of the study. After 20 min of infusion the patient breathed either air or 100% O2 for another 30 min, and the measurements were repeated. Thereafter the inspired gas was shifted to the other FlO2 for 30 min, and a final set of measurements was made. The following day the procedure was repeated using the alternate drug. Aminophylline alone increased FVC and FEV1, but it produced no change in the group in ventilation, hemodynamics, blood gases, or the VA/Q distribution, although individual patients who had low VA/Q areas at baseline showed increases in these areas and worsening of log SD Q. Oxygen alone reduced cardiac output (QT) and caused modest further dispersion of the VA/Q distribution when compared with air breathing during placebo infusion (log SD Q 1.03 +/- 0.27 increased to 1.26 +/- 0.35, p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)