BACKGROUND: Recent information suggests that one of the therapeutic properties of theophylline is an antiinflammatory effect. OBJECTIVE: We evaluated this potential effect of theophylline in eight patients with nocturnal asthma. METHODS: The study design was a randomized, double-blind, placebo-controlled crossover of 2-week treatment periods, separated by a 1-week washout period. Spirometry and bronchoscopy were performed. RESULTS: Theophylline, compared with placebo, significantly improved the overnight decrement in lung function. The higher the nocturnal theophylline level, the greater the improvement in lung function. Theophylline also significantly decreased the percentage of neutrophils in the 4:00 AM bronchoalveolar lavage fluid and stimulated leukotriene B₄ levels from macrophages obtained at 4:00 AM. The greater change in neutrophils correlated with increasing serum theophylline concentration. Also, the change in leukotriene B₄ production was significantly correlated with the theophylline-induced decrement in lavage granulocytes (neutrophils and eosinophils). CONCLUSION: This study suggests that one action of theophylline is to alter inflammatory cell number and function in nocturnal asthma and that it may do this through an leukotriene B₄–mediated mechanism. (J ALLERGY CLIN IMMUNOL 1996;97:1242-6.)