The present studies in the newborn sheep were undertaken to further clarify the mechanism or mechanisms responsible for the early increases in serum thyroid hormone concentrations in the newborn as well as the significance of these changes to newborn nonshivering thermogenesis. Six groups of animals were studied to determine the influence of neonatal cooling, cord cutting, and the effects of thyrotropin-releasing hormone (TRH) and triiodothyronine (T3) injections. Group I newborns were delivered into room air with immediate cord cutting. Group II animals were delivered into room air and cord cutting was delayed 60 min. Group III animals were delivered into a 39° water bath and maintained for 60 min with the umbilical cord intact; the cord was cut at the time of removal from the water bath. Group IV animals were handled similarly to group III animals except that cord cutting was delayed 60 min after removal from the water bath. Group V and VI newborns were handled similarly to group IV animals except that TRH (group V) or T3 (group IV) was injected at the time of removal from the water bath. Deep rectal temperature and serum free fatty acids (FFA), thyroxine (T4), and T3 concentrations were measured in all newborns; FFA was measured as an index of catecholamine release. Serum thyroid-stimulating hormone (TSH) was measured in newborns from groups I and II. The results indicate that the newborn lamb responds to par turition similarly to the human newborn. There are marked increases in mean serum T3 (50 242 μg/100 ml) and FFA levels (245 744 μEq/liter) during the first 60 min with only a transient fall in body temperature (39.1° to 37.4°), indicating effective nonshivering thermogenesis. Serum T4 concentrations do not increase significantly during this time. Warming in the water bath (groups III and IV) prevented the FFA and T3 responses, indicating that parturition per se is not the stimulus to these events. Delayed cord cutting (groups II and IV) produced marked hypothermia (to 35.6 and 34.4°), and the increases in serum FFA and T3 concentrations were not observed until the cord was cut. Mean baseline serum TSH concentrations were 4.7 and 5.3 μU/ml, respectively, in groups I and II animals and increased modestly to peak values at 30-60 min whether or not the umbilical cord was cut. TRH (group VI) did not increase serum T3 levels during the first 60 min, but a significant 4-hr response (to 336 μg/100 ml) was observed. T3 (group VI) did not stimulate the FFA or thermogenic responses directly, but significantly augmented both responses to cord cutting. In addition, there was a significant correlation between serum FFA or T3 concentrations 60 min after cord cutting and minimal rectal temperature (r = 0.53 and 0.71, respectively; P < 0.005). The present results indicate that in the newborn sheep: (I) umbilical cord cutting, rather than cooling, stimulates FFA release, T3 production, and nonshivering thermogenesis; (2) that the early T3 response is not mediated via TRH and TSH, but probably represents increased peripheral monodeiodination of T4 to T3; and (3) catecholamine and T3 probably both play a significant role in newborn nonshivering thermogenesis. The present studies indicate that umbilical cord cutting, rather than cooling, is the stimulus to increased FFA and T3 production and nonshivering thermogenesis in the newborn sheep. The FFA response presumably reflects increased catecholamine secretion. The T3 response probably is due to increased monodeiodination of T4 to T3, and there is preliminary evidence to suggest that this might be mediated by stimulation of tyroxine hydroxylase activity. Thus, increased catecholamine secretion and T3 production, both of which promote nonshivering thermogenesis, might be mediated via adrenergic nervous system stimulation. The mechanism for this stimulation by cord cutting, however, is not yet clear. The present studies also suggest that there are two mechanisms for the thyroidal hyperactivity in response to parturition; an early increase in T3 production due to augmented monodeiodination of T4 to T3; and increased thyroid hormone secretion, mediated by TSH, which more gradually increases serum T4 and T3 concentration during the first 24 hr of extrauterine life.