AimsWe investigated whether the deterioration in asthma control reported following cessation of theophylline was due to tolerance to theophylline. Methods Eighteen subjects with mild stable asthma were given oral theophylline 10 mg kg −1 day −1 or placebo for 2 weeks in a double-blind crossover study. FEV 1 and PD 20 histamine were measured before and 8 h after the first dose of treatment and 8, 32 and 56 h after the final dose. PD 20 AMP was measured before treatment and 9 h after the final dose.Results Six patients did not tolerate theophylline. In the other 12 subjects there were no differences between treatments in daily PEF, symptom scores, rescue bronchodilator use, PD 20 histamine or FEV 1 up to 8 h post treatment. Following withdrawal of theophylline there were significantly lower values for mean FEV 1 (mean difference 0.15 l, 95% CI 0.03, 026) and PD 20 AMP compared to placebo but no difference in other end points.Conclusions The small rebound deterioration in lung function following regular treatment with therapeutic doses of oral theophylline is consistent with the development of tolerance.