Receptor-ligand interactions of fluticasone propionate (FP), a glucocorticoid used for inhalation therapy, were determined and compared with dexamethasone, budesonide, and beclomethasone-17-monopropionate, the active metabolite of beclomethasone dipropionate. Two approaches, evaluation of binding kinetics and competition assays, were applied to obtain relative receptor affinities (RRAs) with dexamethasone as reference. A higher association rate constant and a distinctly lower dissociation rate constant for FP compared with the other glucocorticoids resulted in an equilibrium dissociation constant (Kd) of 0.49 nmol/l. Kd dexamethasone was 9.36 nmol/l; derived RRA of FP was 1910. The calculated half-time of the FP-receptor complex was 10 h, thus exceeding the half-times of all other glucocorticoids as well as their RRAs. Competition assays clearly confirmed the rank order of the tested glucocorticoids, although RRAs were generally lower than those found in kinetic assays and strongly dependent on the assay conditions. The high receptor affinity of FP is reflected by clinical trials demonstrating its superiority to other glucocorticoids. For therapeutic application, the long half-time of the FP-receptor complex should support the practicality of longer dose-intervals.