The aim of the present multicentre, open, randomized, parallel group study was to evaluate the efficacy and safety of salmeterol versus theophylline in asthmatic patients. A total of 112 patients were randomized: 56 received inhaled salmeterol (50 micrograms twice daily) and 50 oral dose titrated theophylline twice daily. The study lasted 12 months. The efficacy of both drugs was evaluated for the first 3 months of the study and the safety for a further 9 months. Spirometric measurements were carried out for the total duration of the study. Salmeterol showed a greater and more significant efficacy than theophylline in reducing both day- and night-time symptoms (P < 0.001) and in reducing additional salbutamol requirement (P < 0.001). The subjective assessment of efficacy by physicians and patients was in favour of salmeterol from the first month of treatment (P < 0.001). Both drugs improved the quality of life as measured by the specific questionnaire 'Living with Asthma' with no significant differences. The total number of adverse events was slightly higher in the theophylline group compared with salmeterol (18 vs 9; P n.s.). Both salmeterol and theophylline increased morning and evening PEFR with no significant difference. FEV1 and FVC increased in both groups of patients; the difference between the effects of the two treatment was not statistically significant at 12 months. Our study suggests that salmeterol has higher efficacy and safety than theophylline in long-term treatment of asthmatic patients.