We studied the duration of the protective effect of azelastine against histamine-induced bronchoconstriction in six subjects with asymptomatic asthma. The study was performed in two periods of five consecutive days each. After a histamine inhalation test, we randomly administered either placebo or a single oral dose of 8.8 mg azelastine in a double-blind crossover fashion. Histamine challenges were repeated 5 hours after ingestion and at 1 pm on the following four days. The geometric means of the dose of histamine (in cumulative breath units [cbu]) necessary to increase specific airway resistance by 100% as compared with baseline (PD 100SR aw) were 8.7 and 8.5 cbu before placebo and azelastine, respectively. Placebo did not significantly influence PD 100SR aw within 99 hours after treatment. Five and 27 hours after azelastine, PD 100SR aw increased to 178.2 and 46.7 cbu, respectively (p < 0.05). Two patients showed a highly significant protection against the airway effect of histamine even 99 hours after ingestion (p < 0.01). These data demonstrate a variable duration of the antihistaminic property of azelastine. The prolonged therapeutic effect in some patients may be beneficial in the timing of medication intervals.