Formoterol is a long-acting beta2-agonist with a rapid onset of effect in patients with chronic obstructive pulmonary disease (COPD), making it potentially suitable for both maintenance and as-needed bronchodilator treatment. To evaluate the efficacy and tolerability of maintenance formoterol in patients with COPD and to compare the effects of additional formoterol as needed with terbutaline. In this 6-month, double-blind study, 657 patients with COPD (40 years, forced expiratory volume in 1s [FEV1] 40-70% predicted normal) were randomized to formoterol 9 microg twice daily (bid) plus terbutaline 0.5 mg as needed (FORM bid), formoterol 9 microg bid plus formoterol 4.5 microg as needed (FORM bid+prn), or placebo bid plus terbutaline 0.5 mg as needed (placebo), all administered via Turbuhaler. Primary efficacy variables were FEV1 and the sum of breathlessness and chest tightness scores combined symptom score. Formoterol significantly (P<0.01) increased FEV(1) compared with placebo: FORM bid 6.5% (95% CI: 2.5, 10.7%); FORM bid+prn 11.8% (95% CI: 7.7, 16.2%). Combined symptom score decreased significantly in both formoterol groups compared with placebo: FORM bid -0.27 (95% CI: -0.49, -0.06; P=0.012); FORM bid+prn -0.32 (95% CI: -0.53, -0.11; P=0.0026). Similar significant (P<0.05) improvements were seen in both formoterol groups for morning peak expiratory flow, cough and sleep scores, and reliever use. In this study, formoterol 9 microg bid via Turbuhaler as maintenance therapy, with either formoterol or terbutaline as rescue medication, provided sustained improvements in lung function and COPD symptoms. Both formoterol regimens were well tolerated with no differences in adverse events or electrocardiogram profiles.