Interaction of histamine and a new histamine H2-receptor blocker, burimamide, was studied in the isolated perfused guinea-pig lung. Histamine induced a rise in perfusion pressure when the lung was perfused with Krebs’ solution. This pressor response was reversed to a depressor effect when mepyramine, H1 -receptor blocker, was added to the perfusing medium. Burimamide competitively antagonized the depressor effect of histamine in the pulmonary vessels. Prior treatment of pulmonary vessels with burimamide alone caused an increase in histamine-induced perfusion pressure. These results suggest that the depressor effect of histamine on pulmonary vascular bed of guinea pig is mediated through the H2-receptors.