Introduction: The aim of this study was to analyze the extracellular matrix and the cellular compartment (fibroblasts, myo-fibroblasts, endothelial cells, histiocytes) in the interstitium of hypoxic myocardium. Methods: We have met again to study our intraoperative myocardial biopsies, the interstitium compartment in over 250 patients with acquired and congenital heart diseases. We have used the following methods: histological (HE, VG, alcian blue, Lie, PAS, Gömöri) immunohistochemicals (α actine of smooth muscle, vimentin, Factor VIII, CD 34) and electronomicroscopical studies. Results: At the ultrastructural level, interstitial active cells were found having a large, indentate nucleous with prominent nucleoli. Their cytoplasm contained a well developed rough endoplasmic reticulum, prominent Golgi complex and a few mitocondria. Some of these cells contain bundles of microfilaments and pinocytic vesicles, becoming bipolar. Immunohistochemically, for mesenchimal structures were positive for vimentin, the histiocites for S-100 protein, the endothelial cells for Factor VIII, and CD 34 and myofibroblasts-like cells for α actine of smooth muscle. Conclusions: The cells lying in the interstitium of the hypoxic myocardium are activated cells having the ultrastructural features of an increased synthesis of secretin. Their presence is related to the degree of the heart failure.