Previous studies have suggested that fetal PRL secretion does not respond to stimuli such as TRH, metoclopramide, and cimetidine. It was postulated that the lack of response to TRH could be due to the possibility that, in the term fetus, lactotropes secrete PRL maximally and would be unresponsive to further stimulation. In order to study this hypothesis, 200 micrograms TRH or saline were administered to preterm pregnant women in labor. Maternal blood was obtained before TRH and saline administration. Maternal and cord blood were obtained at parturition. PRL, TSH, T4 and T3 concentrations were measured in all sera. TRH administration induced a significant increase in maternal serum PRL, TSH and T3 concentrations. In the cord blood of newborns whose mothers received TRH, serum TSH, T4 and T3 concentrations were significantly higher than in cord blood of newborns whose mothers received saline. Cord blood serum PRL concentrations were unchanged after TRH administration. This latter finding suggests that fetal lactotropes do not respond to TRH in the preterm fetus. Desensitization of fetal PRL secreting cells to TRH stimulation and/or the inhibitory effect of elevated fetal circulating corticosteroids on TRH-induced PRL secretion may explain the absent PRL response to TRH during fetal life.