In recent time, it has become more and more probable that patients with severe diffuse coronary artery disease, who are not candidates for aortocoronary bypass surgery or percutaneous transluminal coronary angioplasty procedures, can benefit from transmyocardial laser revascularization (TMR). But the underlying principle of TMR still remains unclear. This study reports on a histological analysis of eight patients, in whom a total of 250 channels had been created, who died after TMR. The TMR channels were created by a CO2 laser surrounded by a zone of necrosis with an extent of about 500 microns. In the hearts of patients who died in the early postoperative period (1 to 7 days postoperative), almost all channels were closed by fibrin clots, erythrocytes, and macrophages. There were no obvious connections between the channels and the ventricular cavity. In specimens from patients, who died 2 or more weeks after the procedure, a granular tissue with high macrophage and monocyte activity was observable. Within this tissue, we observed a developing network of capillaries. Otherwise, the tissue filling the channels did not substantially differ from scar tissue. We failed to observe connections between the ventricular cavity and the new capillaries. Whether these vessels within the closed channels have any impact on myocardial perfusion remains unclear, but it seems unlikely that the clinical effects of TMR are based on the principle of the amphibian heart.