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 Inewborns were delivered into room air with immediate cord cutting.Group IIanimals were delivered into room air and cord cutting was delayed 60 min.Group IIIanimals 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 IVanimals were handled similarly togroup IIIanimals except that cord cutting was delayed 60 min after removal from the water bath.Group VandVInewborns were handled similarly togroup IVanimals 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), thyroxfoe (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 fromgroups IandII.The results indicate that the newborn lamb responds to pat turition similarly to the human newborn. There are marked increases in mean serum T3 (50–242 ng/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 IIIandIV) prevented the FFA and T3 responses, indicating that parturitionper seis not the stimulus to these events. Delayed cord cutting (groups IIandIV) 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, ingroups IandIIanimals 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 firs 60 min, but a significant 4-hr response (to 336 ng/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: (l) 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.