Allergic cutaneous challenge causes mast cell and basophil mediator release which recruit inflammatory cells to the site of antigen administration. This secondary cell infiltration and mediator release is responsible for the changes seen during the late phase of allergic diseases. In this randomised, double-blind, cross-over, placebo controlled study, it was demonstrated that, at steady-state drug concentrations, chlorpheniramine reduced the wheal-and-flare reaction by about 50% compared to the 75% reduction, on average, by cetirizine and ketotifen. Cetirizine significantly reduced eosinophil vacuolisation at all observation periods, i.e. 2,6,10 and 24 h, and also inhibited basophil accumulation significantly at 10 h (75% reduction), while chlorpheniramine had a negligible effect on these variables. These changes would indicate that the late phase reaction was modified, especially as eosinophil vacuolisation is known to correlate with late phase intensity, T-lymphocyte infiltration and subsequent tissue damage. It further supports previous speculation that cetirizine inhibit late histamine release by acting on basophils. The extent of induration in the late phase reaction did not differ significantly among the three treatments. Cetirizine and ketotifen, noticeably although not significantly, reduced eosinophil and lymphocyte recruitment. As these two antihistamines differ structurally and in regard to receptor specificity, it is possible that they exert their actions on other, unspecified, receptors.