Effects of the inhaled corticosteroid budesonide and the oral beta-agonist bambuterol on the nocturnal worsening of asthma were studied in patients with allergic asthma with a circadian peak expiratory flow variation greater than or equal to 15% (group 1, n = 8) and less than 15% (group 2, n = 9). Airflow limitation and airway responsiveness to histamine were measured during 24 hours after 4 weeks of treatment with (A) 0.4 mg budesonide at 8 AM and 8 PM, (B) 20 mg bambuterol at 8 PM, and (C) placebo, in a randomized, crossover design. Patients in group 1 had worse nocturnal symptom scores and a greater airway responsiveness than patients in group 2; in addition, patients in group 1 had a larger increase in responsiveness during the night (1.1 versus 0.6 doubling concentrations [DC]). Both budesonide and bambuterol improved responsiveness more at night than during daytime, thus decreasing circadian variation: at 4 AM, increases in PC20 were 2.0 DC after budesonide and 0.8 DC after bambuterol, compared with placebo. Bambuterol reduced circadian variation in FEV1, but in contrast to budesonide, did not improve 24-hour mean levels of FEV1 and PC20. Both drugs beneficially influenced nocturnal symptoms; the effects of budesonide were stronger than those of bambuterol. Our findings demonstrate that budesonide and bambuterol reduce nocturnal airway responsiveness and asthma symptoms and suggest a relationship between the degree of airway responsiveness and the presence of nocturnal symptoms of asthma.