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Regional changes in cardiac myocyte size resulting from thyroid treatment, and the subsequent reversal of hypertrophy following removal of the thyrotoxic stimulus, were examined. Isolated myocytes were prepared from weight-matched controls and rats treated with desiccated thyroid hormone for 10 weeks. Cells were collected from the right and left ventricles. Cell volume was determined with a Coulter Channelyzer system. Cell length was measured directly using a phase microscope. Myocyte cross-sectional area was calculated from cell volume/length. After 10 weeks thyroid treatment, cell volume was increased in all regions, especially the right ventricle and the epimyocardium of the left ventricle (P less than 0.01). Although cell length was increased in all regions (N.S.), most of the myocyte hypertrophy was due to an increase in cross-sectional area, especially in the right ventricle (P less than 0.01) and epimyocardium of the left ventricle (N.S.). By 2 weeks post-treatment, a substantial regression of myocyte hypertrophy had occurred. However, heart weight was still significantly larger than control (P less than 0.001), due to an incomplete regression of myocyte volume. This study indicates that thyroid hormones stimulate myocyte hypertrophy by increasing both cross-sectional area and cell length. The response is more pronounced in right ventricles than in left ventricles. Within the left ventricle, epimyocardial cells enlarge the most. At 2 weeks post-treatment, cardiac hypertrophy is still present and myocytes have not completely returned to a normal size.