In order to clarify the pathogenetic role of basophils and mast cells in chronic urticaria, histamine and leukotriene (LT)C4 release was examined in washed mixed leukocytes (n = 8) and skin mast cells (n = 5) from patients with chronic urticaria and compared with the same cells from normal controls (n = 9). Anti-IgE-stimulated basophil histamine release was significantly reduced in urticaria patients (median 2.9% vs 15.1% in normal controls), whereas histamine release to A23187, FMLP, and PAF, as well as anti-IgE-induced LTC4 release, showed no differences in both groups. In contrast, anti-IgE-stimulated skin mast cells from urticaria patients reacted similarly to those of controls (median histamine release 11.4% vs 14.2% in normal controls). Pretreatment of the cells with interleukin (IL)-3 upregulated responsiveness of basophil histamine release to anti-IgE in urticaria patients (median histamine release 14.3%), but pretreatment with the H2-antagonist cimetidine showed no effect. These data show that reduced basophil histamine releasability in chronic urticaria is not H2 mediated. It is a stimulus-, mediator-, and cell type-restricted phenomenon that can, at least partially, be reversed in the presence of the cytokine IL-3.