Intravenous injection of platelet activating factor (PAF) in anesthetized guinea pigs induces non-selective airway hyperreactivity. This response to PAF was reduced in a dose-dependent manner by systemic administration of established prophylactic anti-asthma drugs (ketotifen, cromoglycate, aminophylline and glucocorticosteroids) and by competitive antagonists of PAF. These inhibitory effects could not be accounted for by antagonism of histamine (H1), serotonin or peptidoleukotrienes receptors; parasympatholytic activity; cyclo-oxygenase or lipoxygenase inhibition; mast cell stabilization; or bronchodilatation. Infusion or injection of PAF to induce airway hyperreactivity in the guinea pig may provide a prospective test for prophylactic anti-asthma drugs.