A number of structurally different allergens trigger the release of mediators from basophils by cross-linking of IgE receptors. In this study, we analyzed the effects of cyclosporine A (CSA) and FK-506 on allergen-induced histamine release in human blood basophils obtained from birch- or grass-pollen-allergic donors (n = 12). Preincubation of basophils with CSA (0.003-3 microg/ml) or FK-506 (0.003-3 microg/ml) led to inhibition of histamine release induced by purified recombinant tree pollen allergens (r Bet v 1, r Bet v 2) and timothy grass pollen allergens (r Ph1 p 1, r Ph1 p 2, r Ph1 p 5). The effects of CSA and FK-506 were dose dependent, with IC50 values ranging between 0.03 and 0.3 microg/ml for both CSA and FK-506. Cyclosporine H, an inactive CSA analog, did not show any effect on allergen-induced histamine secretion. IgE dependency of the reaction was demonstrated in passive transfer experiments using highly enriched human basophils (> 95% pure) and specific IgE from a patient allergic to Bet v 2. In summary, our data show that CSA and FK-506 inhibit recombinant-allergen-induced histamine release from peripheral blood basophils in allergic donors.