A natural product, kadsurenone, was isolated from the Chinese herbal preparation haifenteng (Caulis piperis futokadsurae) and characterized as an orally-active specific antagonist of the platelet-activating factor (PAF). Kadsurenone inhibits the specific binding of 3H-PAF to a receptor preparation from rabbit platelet membrane in a competitive and reversible manner, its Ki being 3.88 X 10(-8) M. It inhibits the aggregation of rabbit platelets in plasma induced by PAF with a pA2 of 6.28, but not those induced by arachidonic acid, epinephrine, ADP or A-23187. It inhibits the aggregation of isolated human neutrophils with a pA2 of 6.32. It also inhibits PAF-induced degranulation and release of beta-D-glucuronidase at 2-24 microM in vitro. In the rat, kadsurenone at 8-40 mg/kg i.p. inhibits the increases of plasma lysosomal enzymes and haematocrit induced by intravenous PAF. In the guinea pig, kadsurenone at 25-50 mg/kg p.o. reduces the increase of cutaneous vascular permeability induced by PAF. These results indicate that kadsurenone is a specific and effective receptor antagonist of PAF in several in vitro and in vivo systems.