The pathology of pulmonary hypertension in man is based on the migratory behaviour of the vascular smooth muscle cells of the media. In states of chronic hypoxia, as seen in chronic obstructive lung disease and in native highlanders, there is a limited migration of mature-looking muscle into the intima. Here it produces a layer of longitudinal muscle, the formation of muscular tubes and muscularization of pulmonary arterioles. In congenital septal defects, primary pulmonary hypertension and rare cases of hepatic cirrhosis there is free migration of altered, electron-dense muscle cells into the intima and lumen through gaps in the inner elastic lamina. This migration of 'dark' smooth muscle cells is associated with increased numbers of pulmonary endocrine cells containing gastrin-releasing peptide in the terminal and respiratory bronchioles. In rats, hypoxia or pyrrolizidine alkaloids induce vasoconstriction with muscular evaginations but no migration of smooth muscle cells. As a consequence, the rat is a poor animal model for pulmonary hypertension. Pulmonary vasodilators are unlikely to be effective once migration of vascular smooth muscle cells has occurred.