It has been previously shown that inhaled salbutamol (S) and intravenous aminophylline (A) have an additive effect as bronchodilators in patients with chronic obstructive pulmonary disease (COPD). This additive effect could be due to different modes of action or different distributions of drug. In order to investigate the additive effect of S and A when administered by the same route, we studied eight patients 63.4 +/- 1.84 yr of age (mean +/- SEM), with long-standing COPD (FEV1, 0.96 +/- 0.12 L) by giving them intravenous A and S. A double-blind, cross-over study was performed on two separate days by administering either A followed by S or vice versa. Each drug when given alone increased the FEV1 significantly (p less than 0.01). The mean increase was 0.17 +/- 0.06 L (18% of baseline) for S and 0.15 +/- 0.05 L (17% of baseline) for A. The FEV1 increased 0.07 +/- 0.02 L when S was added to A (95% confidence interval, 0.02 to 0.12, 7% of baseline), and when A was added to S 0.05 +/- 0.03 L (95% confidence interval, -0.02 to 0.12, 6% of baseline). Neither change was significant. Heart rate (HR) was increased significantly (p less than 0.01) by S (22 +/- 3.4%), but not by A when it was given first. However, addition of the second drug increased HR significantly (p less than 0.01) from HR with one drug alone; the mean increase was 31 +/- 8.5% of baseline with the addition of S, and 19 +/- 4.06% of baseline with the addition of A.(ABSTRACT TRUNCATED AT 250 WORDS)