The placenta has recently been shown to express the transporters for catecholamines and serotonin. In previous studies of catheterized fetal sheep, we used isotope tracer methods to show that the placenta contributes to>50% of total (fetal+placental) clearance of norepinephrine. Using norepinephrine transport blockers, we demonstrated that more than 50% of placental clearance is norepinephrine transporter dependent. The factors which regulate expression of these proteins in the placenta are not known. To compare placental transporter expression with alterations in placental function during pregnancy, we used the human norepinephrine cDNA to examine RNA extracted from the placenta of 35 patients following complicated and uncomplicated pregnancies. To compare transporter expression and its relation to fetal condition at birth, we collected both placentas and umbilical arterial cord blood for catecholamines and blood gases. Transporter expression was measured by Northern analysis and RNase protection. Quantitative norepinephrine transporter expression was compared to umbilical plasma norepinephrine by regression analysis. Uncomplicated pregnancies had a higher level of placental norepinephrine transporter expression than complicated pregnancies. An inverse relationship between umbilical cord norepinephrine level and transporter expression was demonstrated. That is, if transporter expression was high, umbilical plasma norepinephrine levels were low (r=0.54, p<0.01). We conclude that derangements in placental catecholamine clearance may be important in the pathophysiology of pregnancy disorders associated with placental dysfunction, impaired placental blood flow or intrauterine growth retardation. This may also explain the adverse effect of drugs, such as cocaine, which block catecholamine transport.