The aim of the study was to alter the vascular endothelium of the mammalian myocardium with respect to coronary flow regulation and vascular permeability. For this purpose, carbogen gas perfusion (GP) of Langendorff-type isolated rat and guinea pig heart was chosen. Perfusion of the hearts with carbogen gas was possible, as well as replacement of the GP by fluid perfusion. The energetic and mechanical state, the creatine kinase release, and the electron microscopic examination of the rat heart indicated only a moderate to minimal alteration of the cardiomyocytes after GP. As a result of GP a massive alteration of the vascular endothelium could be demonstrated in the rat heart, based on the release of the cytosolic endothelial marker enzyme, purine nucleoside phosphorylase, the partly altered vascular permeability and the morphologically detected endothelial damage to arterioles, capillaries and venules. Moreover, the reduced coronary flow response to short periods of anoxia (rat, guinea pig) and the inverted flow response to serotonin administration with maintained response to sodium nitroprusside (rat) in the post-gas perfusion period reflected an alteration of endothelial smooth muscular interaction in the rat and guinea pig heart. Furthermore, the distensibility of the coronary vasculature was increased in the rat and guinea pig heart in the post-gas perfusion period, where a relative autoregulatory behavior was maintained (rat) or partly maintained (guinea pig) in passively predilated vessels. In conclusion, carbogen gas perfusion of isolated hearts allows to induce preferred alteration of endothelium and endothelium-smooth muscle interaction.