The roles of thyroid and growth hormone, and food restriction in maintenance of heart mass and in carbon monoxide-stimulated cardiac growth were examined. First, thyroidectomized and normal adult male rats inhaled up to 500 ppm CO in air for 42 days. Combined ventricular weights of thyroidectomized rats inhaling CO and air were 12 and 23% smaller than predicted, respectively, while the combined ventricular weight of normal rats inhaling CO was 29% larger than predicted. Thyroidectomy increased the mass of the left ventricle relative to the right ventricle; this was reversed by CO treatment. While the hematocrit increased in thyroidectomized–CO rats, it was lower than in normal–CO rats: likewise the hematocrit of thyroidectomized–AIR rats was lower than that of normal rats in air. Body weights of the thyroidectomized rats were 57% that of normals. As additional controls, two groups of normal rats (one AIR, one CO) were maintained at the same body weight as the thyroidectomized rats, by adjusting food intake. Combined ventricular weight was less than predicted in AIR rats and failed to increase in CO animals, while hematocrits were the same as normals in air and in CO. Serum thyroxine (T4) and growth hormone levels assayed in thyroidectomized rats were less than 15 and 25% of normal rats, respectively. Growth hormone levels were not altered by CO inhalation in thyroidectomized and in normal rats. Levels of both hormones were normal in food-restricted rats. While thyroidectomy produced cardiac atrophy, cardiac growth was stimulated by CO inhalation, although heart mass then only approached that of normals in air. Food restriction also produced cardiac atrophy, but CO inhalation failed to stimulate heart growth.