This multicentre study was set up to compare the efficacies of two long-acting beta 2-agonists, oral bambuterol (20 mg nocte) and inhaled salmeterol (50 micrograms b.i.d.), for the treatment of moderate to severe asthmatics who were considered to be on optimal steroid/bronchodilator therapy, but continued to have troublesome nocturnal symptoms. The study was of double-blind, parallel-group design and comprised a 2-week run-in on previous maintenance therapy followed by a 6-week study treatment period. There were 117 randomized asthmatic patients aged 20-70 years (65 women and 52 men with a mean age of 45 and predicted FEV1 of 64%), who had been taking 800-2000 micrograms inhaled steroid and/or up to 20 mg oral steroid per day for at least 4 weeks. They were asked to complete daily diary cards, recording morning and evening PEF, daily symptoms, nocturnal awakenings, rescue medication and subjective tremor. There was a significant increase in both morning and evening PEF respectively, on bambuterol (28 l min-1, 20 l min-1, P < 0.05) and salmeterol (29 l min-1, P < 0.001; 23 l min-1, P < 0.01) when compared with run-in. The mean percentage fall in overnight PEF was reduced by 8.3% (P < 0.001) on bambuterol and by 6.8% (P < 0.001) on salmeterol. Nocturnal awakenings and daytime symptoms due to asthma were significantly lowered by both treatments, as was the consumption of rescue bronchodilator. Tremor scores were very low during both run-in and study treatments. No significant treatment difference between bambuterol and salmeterol was detected for any of the above variables. Once-daily oral bambuterol provides a highly effective alternative to twice-daily inhaled salmeterol for relief of nocturnal symptoms in patients with moderate to severe asthma.