The efficacy and tolerability of salmeterol, 50 micrograms b.i.d. was compared for three months with salbutamol, 200 micrograms q.i.d., administered from metered-dose inhaler. For the following nine months, safety and clinic lung function was monitored on salmeterol, 50 micrograms b.i.d., compared with salbutamol, 200 micrograms b.i.d. This comparison was made in a multicentre, double-blind, parallel-group study of 667 moderate asthmatics, who had a forced expiratory volume in one second (FEV1) or peak expiratory flow rate (PEFR) > 50% predicted, a 15% reversibility to inhaled salbutamol and who were experiencing symptoms. Throughout the first three month treatment period, both morning and evening PEFR were significantly higher on treatment with salmeterol than salbutamol (mean differences between the treatments 30 l.min-1 for morning, p < 0.001, and 11 l.min-1 for evening, p < 0.01). In addition, the diurnal variation in PEFR, nocturnal and daytime symptoms and use of additional salbutamol were significantly lower in the salmeterol treated group. This improvement was also apparent in the separate subpopulations of patients taking no concurrent glucocorticosteroid or concurrent inhaled and/or oral glucocorticosteroids. Both treatments were well-tolerated throughout the 12 months of treatment. There was a lower incidence of asthma and related events during salmeterol treatment compared to salbutamol treatment subgroups. The results of the study clearly demonstrate that salmeterol, 50 micrograms b.i.d., is well-tolerated and more effective than salbutamol, 200 micrograms q.i.d., in the treatment of moderate asthma.