Guinea pig hearts isolated by the Langendorff technique were perfused with a nitro-blue tetrazolium salt solution. In spite of a homogeneous dark-blue staining at the macroscopic examination, light-microscopic studies showed a spotty staining of the myocardial fibers. Since no microscopic alterations were found which could explain the unstained areas, ultramicroscopic studies were undertaken. At ultrastructural level, striking alterations of myocardial cells were observed. They consisted of mitochondrial lesions, alterations of the transversal tubuli, and intercalated discs. Arteriolar narrowing and capillary edema were found, suggesting that pathological changes in the microcirculation could be a possible reason for the spotty staining of the myocardial fibers. Some speculations on the nature and localization of the formazan granules are also reported.