Premature labor is one of the most common complications associated with cocaine abuse during pregnancy. Still, the effect of cocaine on the pregnant uterus is largely unknown. Although inhibition of neuronal uptake is the most important effect of cocaine in most tissues, after mid-pregnancy, the uterus has few functioning adrenergic nerve endings. To determine whether cocaine has any effect on uptake during pregnancy, we evaluated the ability of the term pregnant human uterus to take up [3H]-norepinephrine (9 × 10−8 mol/L) and the ability of cocaine (10−6–10−8 mol/L) to block this uptake. Because d-propranolol has been shown to block the direct effects of cocaine on the pregnant rabbit uterus, we also evaluated the ability of d-propranolol (2 × 10−6 mol/L) to block the effect of cocaine on catecholamine uptake. The ability of the Uptake 2 inhibitor hydrocortisone (2 × 10-5 mol/L) to block catecholamine uptake was also studied. We found that [3H]-norepinephrine was taken up by both the pregnant myometrium and endometrium, and that cocaine blocked this uptake by up to 55% at concentrations as low as 10−7 mol/L. D-propranolol had no effect on the ability of cocaine to block catecholamine uptake. Hydrocortisone blocked uptake by the endometrium by 15% but did not block uptake by the myometrium. We conclude that the pregnant human uterus at term retains the ability to take up catecholamines and that cocaine blocks this extraneuronal uptake. This may explain, in part, the association of cocaine use with premature labor. © 1991 by The American College of Obstetricians and Gynecologists.