The present experiments were designed to study the effects of levocetirizine (a potent selective histamine H₁ antagonist) on the contraction induced by histamine on isolated rabbit bronchioles using the precision-cut lung slice technology. Histamine induced a concentration-dependent contraction of isolated rabbit bronchioles (pD₂ value of 5.6). Mepyramine (0.01–1 µmol/l) induced a shift to the right without any decrease in the concentration-response curve to histamine (pA₂ value of 8.2). Levocetirizine (0.03–0.1 µmol/l) induced both a shift to the right and a decrease in the maximal amplitude of the concentration-response curve to histamine (pA₂ and pD′₂ values of 7.9 and 7.0, respectively). The difference between both compounds could be explained in terms of the difference in the dissociation rate from the histamine H₁ receptor coupled to a putative low receptor reserve present in the rabbit bronchioles.