1 Seven atopic subjects received two injections of antigen and one of saline intradermally in the back on each of 4 separate days. They were pretreated with four different drug combinations: (a) adrenaline 0.3 mg subcutaneously over the deltoid muscle (b) subcutaneous adrenaline preceded by 5 mg of the specific ,32-adrenoceptor antagonist ICI 118,551 orally (c) 8 mg of salbutamol orally (d) placebo. Tablets were given 2 h before and subcutaneous injections 15 min before the intradermal injections of saline and antigen. 2 The median flare response to intradermal low dose antigen and high dose antigen after pretreatment with adrenaline was 4% and 49% of the response seen following pretreatment with placebo (P < 0.001). When adrenaline was preceded by ICI-118,551, the corresponding median flare responses were 2% and 44% (P < 0.001) of the placebo response. The flare response after pretreatment with salbutamol was not significantly different from placebo.3 Adrenaline suppressed the median weal response to the higher dose of antigen to 52% of the response after pretreatment with placebo (P < 0.05). This suppression by adrenaline was blocked by pretreatment with ICI 118,551. The median weal response after the highest dose of antigen was suppressed by salbutamol to 66% of the response seen after placebo, although this was not significant even when a further three subjects were studied with either salbutamol or placebo. 4 These results confirm that a small dose of systemic adrenaline attenuates the weal and flare response to intradermal antigen. This suppression of the weal response is blocked by a P2-adrenoceptor antagonist although it is only partially mimicked by high dose oral salbutamol. The suppression of the flare response may involve a-adrenoceptor stimulation.