Urticarial reactions are characterized by dermal capillary dilatation and edema, associated with a variably intense mixed inflammatory infiltrate consisting of neutrophils, eosinophils, T-helper lymphocytes, and activated macrophages. Mast cell numbers are moderately increased by a factor of 2.4, in contrast to mastocytosis where numbers are much higher (5-48-fold increase). In urticarial vasculitis there is in addition endothelial damage, leukocytoclasia, and fibrin and complement deposition. The emigration of leukocytes is regulated by vasoactive and chemotactic mediators released firom mast cells, inducing a sequential upregulation of endothelial adhesion molecules (P-selectin, E-selectin, ICAM-1, and VCAM-1), of beta2-integrins on leukocytes, and of cytokines on endothelial, epithelial, and infiltrating cells. In nonlesional skin, there is also an increase of mast cells and an upregulation of endothelial adhesion molecules, probably due to molecules in the circulation of which P-selectin and TNFalpha have so far been demonstrated. Whereas these data provide a molecular basis for the understanding of variations in mast cell-dependent pathology, they underline the fact that they are not diagnostic for different types of urticaria, except for urticarial vasculitis and mastocytosis.