The possible antagonistic effect of the beta 2-adrenoceptor agonist salbutamol and the methylxanthine theophylline on allergen-induced immediate skin reactions was elucidated. Dose-dependent reductions of early allergen-induced responses (flare and weal) were produced in eight atopic patients by salbutamol, 2.5 ng-1 micrograms (p less than 0.001). Theophylline attenuated these responses only at a high dose, 100 micrograms (p less than 0.01). Histamine-induced flare responses were not influenced by these agents, but wealing was inhibited by 35% by 1 microgram of salbutamol (p less than 0.001). It is concluded that agents which interact with anaphylactic histamine release and elevate cyclic AMP level in heterogeneous tissues in vitro have similar counteracting effects on allergen-induced skin reactions in atopic subjects.