Basophils in mononuclear cell populations were challenged with allergens, anti-immunoglobulin E (anti-IgE), C5a or formyl-methyl-leucyl-phenylalanine (FMLP), with or without a short pre-incubation with interleukin-3 (IL-3), in the presence of increasing concentrations of terfenadine. At doses of 0.1-1 micrograms/ml, terfenadine inhibits histamine release and generation of the sulfidoleukotrienes, leukotriene C4, D4 and E4 in basophils challenged with an IgE-dependent trigger. At concentrations above 10 micrograms/ml, however, terfenadine induces the histamine release but abolishes the formation of leukotrienes, and this may be due to a cytotoxic effect. In eosinophils, by contrast, terfenadine appears to inhibit the production of leukotrienes by eosinophils, triggered by FMLP only at concentrations above 10 micrograms/ml (which are toxic to basophils at least). In a double-blind, placebo-controlled study, 15 allergic patients were given skin challenges with specific allergen and with histamine, before and at 3 days, 2 and 4 weeks after treatment with terfenadine (120 mg/day for 3 days). The skin reactions were evaluated visually and followed kinetically by thermography. Terfenadine caused a significant decrease in both the immediate and late-phase reactions. Late-phase reactions to histamine were shown with thermography in some of the patients tested.