The efficacy of bronchodilator therapy was assessed in the long-term management of patients with chronic bronchitis and varying degrees of reversible air-flow obstruction. Twenty-five patients with a mean forced expiratory volume in one second (FEV1) 38.7% predicted received: optimized doses of orally administered, sustained-release theophylline, inhaled salbutamol (200 micrograms 4 times a day), a combination of the 2 drugs, and identical placebo therapy for periods of 3 wk in a randomized, double-blind, crossover trial. Patients who deteriorated during treatment were assessed immediately and designated "treatment failures" if additional therapy proved necessary. Such "failures" occurred in 9 patients with placebo, in 8 with salbutamol, in 6 with theophylline, and in only 1 with combined therapy. Using a ranking system based on "treatment failures" and mean daily peak flow rates, first preference was given to combined therapy in 13 patients, theophylline in 6, salbutamol in 4, and placebo in 2. Thus, both combined therapy (p less than 0.001) and theophylline (p less than 0.05) were better than placebo, but this was not so for inhaled salbutamol. Objective improvements in FEV1 and forced vital capacity were a consistent finding with combined therapy compared with placebo, although not with single agents, and additive effects were clearly demonstrated. In the subgroup of patients able to tolerate placebo therapy, no subjective benefit could be discerned during any of the 3 periods of active treatment. Thus, the combination of orally administered, sustained-release theophylline and inhaled salbutamol offered significant advantages in the clinical control of patients with chronic bronchitis with air-flow obstruction.