We investigated the effect of cyclosporin A (CsA) on in vitro release of chemical mediators from mast cells purified from human lung tissues. CsA (3 X 10(-2) to 1 microgram/ml) dose-dependently inhibited IgE-mediated release of histamine and peptide leukotriene C4 (LTC4) from human lung mast cells. The same concentrations of CsA also inhibited the release of histamine from lung mast cells challenged with the Ca2+ ionophore A23187. Therefore, CsA in pharmacological concentrations inhibits the IgE- and non-IgE-mediated release of inflammatory mediators from mast cells purified from human lung tissues.