The mechanisms of action of cyclosporin A require further elucidation since this drug includes anti–inflammatory properties unrelated to its previously documented effect of T cells. A study was performed using enzymatically dispersed cells from nasal polyps of 7 subjects to examine the effects of cyclosporin A on the release of histamine, leukotriene C₄/D₄ (LTC₄/D₄) and thromboxane (TxB₂) following stimulation by anti–IgE. Cells were resuspended and preincubated with cyclosporin A (0.1, 1 and 10 μM) or 0.1% DMSO (the vehicle used to dissolve cyclosporin A) for 20 min prior to challenge with 10 μg/ml ε–chain–specific anti–IgE for 45 min at 37°C. Histamine, LTC₄/D₄ and TxB₂ were measured using EIA. Cyclosporin A significantly inhibited the release of histamine, LTC₄/D₄, and TxB₂ in a concentration–dependent manner. IC³⁰ values, histamine (5.1 μM), LTC₄/D₄ (7.8 μM) and TxB₂ (6.2 μM), were determined. These data demonstrate new antiallergic properties of cyclosporin A using a novel in vitro model which mimics more closely allergic inflammation.