This paper reports on partial purification and characterization of a natural (endogenous) factor capable of inhibiting in vivo DNA synthesis in mouse pneumocytes in a tissue-specific manner. By using a combination of ultrafiltration and various chromatographic techniques, the active agent has been partially purified from aqueous extracts of both bovine and rat pulmonary tissue. The factor responsible for the observed effect was found to be a heat labile compound, most likely a protein of approx. 40 000 molecular weight. Its chemical and physicochemical properties determined so far, and also the manner of its biological action implies that this lung tissue derived agent might be an endogenous proliferation inhibitor with a chalone-like character operating in the pulmonary epithelial cells.