The effect of thyrotropin-releasing hormone (TRH) on the mechanism regulating growth hormone (GH) secretion was investigated in urethane- anesthetized male rats. The iv injection of TRH (0.2 and 3 µg/100 g BW) caused a significant and dose-related increase in plasma GH. Greater GH responses to TRH were not obtained with doses of TRH larger than 5 µg/100 g BW. TRH injection also raised plasma GH in rats subjected to hypothalamic ablation, in which the maximum increments of plasma GH after TRH injection were greater than in control rats. Plasma GH responses to the iv injection of chlorpromazine (200 µg/100 g BW) were significantly augmented by the concomitant iv injection of TRH in a dose of 3 µg/100 g BW. However, a large dose of TRH (25 µg/100 g BW) injected with chlorpromazine caused a significantly smaller increase in plasma GH than did smaller doses of TRH (0.2 and 3 µg/100 g BW). TRH injection into the lateral ventricle (0.02 and 0.2 µg/100 g BW) inhibited significantly the GH release induced by chlorpromazine, whereas TRH (0.2 µg/100 g BW) alone caused only a slight increase in plasma GH. These results suggest that TRH may not only stimulate GH release by a direct action on the pituitary, but may also modify GH secretion by acting through the central nervous system. (Endocrinology98: 1047, 1976)