To assess additive effects of therapy with salbutamol and theophylline, we examined 16 patients (5 women, 11 men) with a mean age of 67.6 +/- 6.9 (SE) yr, long-standing chronic obstructive pulmonary disease, an FEV1 of 0.73 +/- 0.05 (SE) L, and a smoking history of 38.4 +/- 4.1 (SE) pack-years. On 2 consecutive days they were given large doses of either salbutamol followed by theophylline or vice versa. In the group as a whole, responses to salbutamol alone averaged 24% of the baseline FEV1 and responses to theophylline alone were 17% of baseline. Similar increases were observed when either drug was given after the other; responses to the 2 agents were additive. Responses to salbutamol were larger (p less than 0.05) than those to theophylline. Responses to salbutamol and theophylline were correlated. In 8 patients whose FEV1 increased after salbutamol by more than both 20% and 0.2 L, adding theophylline produced responses that were also large (32% baseline and 0.22 L). In the remaining 8 nonresponsive patients, salbutamol and theophylline were also additive, but the small (mean 10% or 0.06 L) increases in FEV1 with theophylline raised the question of the risk benefit ratio of high-dose theophylline therapy in such patients.