OBJECTIVE Our purpose was to determine the transplacental transfer of thyrotropin-releasing hormone at the time of fetal blood sampling. METHODS Four hundred micrograms of thyrotropin-releasing hormone was given intravenously to 13 pregnant women between 24 and 35 weeks' gestation and maternal-to-fetal transfer of thyrotropin-releasing hormone was determined at fetal blood sampling 1 to 93 minutes later. The fetal thyrotropic response to thyrotropin-releasing hormone was determined by measuring thyroid-stimulating hormone, thyroxine, and prolactin. For comparison, endogenous fetal and maternal levels of thyrotropin-releasing hormone, thyroid-stimulating hormone, thyroxine, and prolactin levels were determined in a further 20 patients undergoing fetal blood sampling between 19 and 35 weeks' gestation. The concentration of thyrotrophin-releasing hormone was measured by radioimmunoassay and thyroid-stimulating hormone, thyroxine, and prolactin by chemiluminescence assay. RESULTS Thyrotropin-releasing hormone was undetectable in the maternal circulation, whereas endogenous levels were detectable in the fetus from 19 weeks' gestation (median 150; range 50 to 276 pmol/L) and did not correlate with gestational age. After thyrotropin-releasing hormone injection as an intravenous bolus, peak levels in the mother were attained at 3 minutes (50,000 pmol/L). Maximal transplacental transfer of thyrotropin-releasing hormone occurred within 5 minutes of maternal administration but accounted in fetal blood for only 0.01% of initial dose administered (median 250; 30 to 550 pmol/L). Thyrotropin-releasing hormone-stimulated fetal peak thyroid-stimulating hormone levels occurred within 13 minutes and were higher than maternal values (p < 0.001). There was no change in fetal prolactin level with thyrotropin-releasing hormone therapy. CONCLUSIONS Although maternally administered thyrotropin-releasing hormone crosses the placenta sparingly, it still elicits a thyroid-stimulating hormone but not a prolactin response in the human fetus.