We determined the placental transfer of TSH in anin vitromodel of dually perfused isolated lobule in 28 human term placentas by adding varying concentrations (5-60 μIU mL-1) of TSH as a single bolus dose to the closed maternal circulation. Transmembrane transfer of TSH was also studied by adding 45 μIU mL-1to the maternal or fetal compartment of a dual chamber of fetal membranes in culture. Passage of freely diffusible markers creatinine and antipyrine were also studied in this model. TSH concentration was measured by third generation chemiluminescence assay with a sensitivity of 10 mIU mL-1. In the perfusion experiments, at physiologic concentrations the slow decline of TSH in the maternal circulation was associated with a small linear increase in fetal levels to 0.11 ± 0.04% of initial dose at 2 h. The placental transfer rate was 0.08 μIU min-1. Increasing maternal concentrations of TSH were associated with proportional increases in transfer rate (y= 0.002x; R2= 0.99) and placental uptake (y= 0.01x; R2= 0.97). The placental permeability of TSH was 2.4·10-4mL min-1g-1and was proportional to its coefficients of diffusion in water and molecular size. The transmembrane transfer and permeability of TSH was comparable to those of the placenta. We conclude that TSH crosses the human term placenta and fetal membranes sparingly.Abbreviations: MAUC,maternal area under the curve;FAUC,fetal area under the curve;F/M,fetomaternal;TRH,TSH-releasing hormone