Hormone responses to a bolus injection of thyrotropin releasing hormone (TRH) were studied in 8 newborn lambs between 6 and 19 hours of age. The effect of a bolus injection and 45 min infusion of somatostatin (SRIF) on these responses was studied in 2 other animals. Serial measurements of serum TSH, prolactin, triiodothyronine (T3) and thyroxine (T4) were conducted for 2 to 6 h in all animals. Mean baseline T4 and T3 concentrations were 12.6 microng/dl and 221 ng/dl, respectively, both significantly higher than values in fetal or adult animals. These high values were due to the events of parturition. In spite of the high baseline T4 and T3 levels, there were rapid and significant increases in both TSH and prolactin concentrations in response to TRH alone. The TSH response evoked further increments in serum T3 and T4 concentrations observed at 30 min and 60 min, respectively, both subsequently increasing progressively through 6 h. During the 45 min period of SRIF infusion, the TSH T4 and T3 responses to the zero time TRH injection were minimal. However, after discontinuing SRIF, late increases in TSH, T4 and T3 were observed. The results indicate that the hyperiodothyroninemia characteristic of the newborn period does not block the response to exogenous TRH, whereas the inhibitory effect of exogenous SRIF is observed in the newborn as in the adult. The increased endogenous TRH secretion presumably responsible for the neonatal TSH surge may be overriding the negative feedback effect of thyroid hormones.