For centuries, Ganoderma lucidum has been used in Oriental medicine for the treatment of chronic bronchitis. Sequential fractions of the culture medium of this plant revealed that one of the active constituents was cyclooctasulfur. The latter effectively inhibited histamine release from rat peritoneal mast cells and impeded 45Ca uptake into these cells without affecting the cyclic AMP content. SDS-PAGE analysis indicated that cyclooctasulfur induced some changes in protein bands obtained from the membrane fraction of mast cells, suggesting that this compound interacts with membrane proteins so as to inhibit 45Ca uptake, and that this may be the main cause of histamine release inhibition.