The relative benefit of maintenance therapy with theophylline, inhaled albuterol, and the combination was examined in 18 adolescents and adults with chronic asthma during a 3-month, randomized, double-blind, crossover trial. Theophylline and combination regimens were associated with significantly fewer days with symptoms (52% and 55%) than albuterol (72%). The greater frequency of symptoms during the albuterol regimen was increasingly apparent more than 4 hours after albuterol doses and was greatest between 4 and 8 A.M. Albuterol transiently inhibited histamine-induced bronchospasm to a much greater degree than did theophylline, and combining the drugs produced at least an additive effect. The effect of albuterol was completely absent by 4 hours, however, whereas that of theophylline persisted. Thus, in spite of greater acute effects on the airways, the transient duration of effect from inhaled albuterol appears to limit its usefulness as maintenance therapy, especially for patients with nocturnal symptoms.