1. In isolated guinea-pig lungs perfused through the pulmonary artery, histamine caused a rise in perfusion pressure which was converted to a fall by a prior injection of mepyramine.2. Evidence is provided to show that at least part of the histamine effect was due to its direct action on pulmonary vascular tissue, and was largely independent of bronchomotor tone.3. Neither the pressor nor the depressor effects were modified by adrenoceptor blocking agents, phentolamine and propranolol, in doses which reversed or blocked the effects of noradrenaline, adrenaline or isoprenaline. The actions of histamine could therefore not be attributed to catecholamine release. The involvement of cholinergic mechanisms was also excluded since atropine failed to influence the histamine effects.4. It is suggested that the mepyramine-sensitive pressor, and the mepyramine-resistant depressor effects of histamine, were mediated by different receptors.5. It is proposed that a vasodilator action of histamine leading to a partial obstruction of the pulmonary airways could be part of the explanation for the relative ineffectiveness of mepyramine in blocking anaphylactic bronchoconstruction in the guinea-pig.