Beta‐adrenoceptor stimulating agents possess anti‐allergic effectsin vitroandin vivo.To study the site of action further 15 atopic subjects were pretreated with 1 μg terbutaline injected intradermally (i.d.) followed by allergen challenge. Other skin sites challenged without such pretreatment served as controls. At different time intervals the skin was rechallenged with the same allergen, dissimilar allergen, or the histamine liberating agent, compound 48/80. In addition terbutaline was injected i.d. alone followed by allergen challenge at different time intervals to determine the duration of the anti‐allergic effect.Pretreatment of the skin with 1 μ‐g terbutaline inhibited skin reactions to subsequently injected allergen with approximately 80% (flare) and 60% (wheal) (P<0.001) as compared with control. The inhibitory effect of terbutaline on the wheal and flare response to allergen was found to last up to 8 h (P<0.01). Rechallenge with the same allergen or a dissimilar challenging agent resulted in a reduced skin reaction compared with control challenge (P<0.01). Skin challenged with allergen in the presence of terbutaline gave a diminished response on rechallenge with the same allergen 24 h later, whereas rechallenge with an unrelated allergen or compound 48/80 produced a response similar to that of the control. The results suggest that allergen challenge in the presence (or absence) of terbutaline desensitizes the mast cells to further challenge with the same allergen and that terbutaline is capable of preventing mediator depletion of skin m