We have developed a guinea pig model of cigarette smoking induced lung disease, whereby animals exposed for several months to cigarette smoke develop emphysematous lung destruction as well as mild pulmonary hypertension with increased muscularization of the arterioles. To ascertain whether the animals with pulmonary hypertension had structural alterations of the right ventricle, we morphologically determined the volume proportion of inflammatory cells, fibrosis, and muscle cytoplasm and nuclei, and compared these values to those of age matched animals not exposed to smoke. We found that there was a significantly increased volume proportion of both fibrous tissue and inflammatory cells in the subendocardial myocardium after 12 months of cigarette smoke exposure, but not after 3 or 6 months. Since the degree of pulmonary hypertension, and the weight of the right ventricle were similar at the 3 time periods, we conclude that the inflammatory cell infiltrate and fibrosis in the subendocardial myocardium are manifestations of long term pulmonary hypertension, rather than any indication of co-existant damage to the myocardium as a result of the smoke exposure. These features would be compatible with the "right ventricular hypothesis" of Morrison (8) for the development of cor pulmonale, with the pathological changes seen as a result of a dysequilibrium between oxygen supply and demand in the right ventricle.