The capacities of D- and L-thyroxine to induce cardiac hypertrophy have been studied in rats as a function of the extent of the circulatory changes produced by the two isomers. D-Thyroxine had no effect on blood pressure, heart rate, or cardiac output, but significantly increased heart mass. L-Thyroxine had a small effect on mean blood pressure, a larger effect on heart rate, and caused a large increase in cardiac output. The closest parallels were between effects on heart rate and on heart growth. In companion experiments, D- and L-thyroxine were shown to be equipotent in stimulating atrial protein synthesis in vitro. The growth-promoting effects of both D- and L-thyroxine, therefore, seem largely direct and independent of the large increase in flow work produced by administration of the L-isomer in vivo.