The reproducibility of the histamine challenge in seven asymptomatic patients with extrinsic asthma, provoked four times each with 1-2 weeks interval, was investigated. The method was thereafter used in order to find the sub-threshold bronchodilating dose of a new beta-agonist KWD 2131 with a preferably anti-allergic property. Selection of patients and methodology of the histamine challenge procedure were carefully standardized. Histamine was administered during quiet breathing at 3-min intervals in a step-wise cumulative manner up to a point where greater than 20% decrease in FEV 1.0 was reached. The pooled intra-individual standard deviation was 4.6% in FEV 1.0, 5.0% in PEFR, and 4.7% in FVC. Pretreatment with KWD 2131, before histamine challenge, showed that the subthreshold dose for bronchodilatation was 0.5 mg in nine patients and 0.25 mg in three patients compared with 1 mg in patients with intrinsic asthma. It was important to perform individualized dose-titration of the sub-threshold bronchodilating dose of KWD 2131 before initiation of a subsequent allergen provocation study.