Cocaine use in pregnancy is associated with a premature labor rate as high as 50%, but little is known about its effect on uterine contractility. To determine whether cocaine directly augments pregnant uterus contractility, uterine strips from 27-day pregnant New Zealand White rabbits (term, 31 days) were exposed to cocaine alone (30 μmol/L) or cocaine plus epinephrine (10-9 to 10-5 mol/L) or oxytocin (10-10 to 10-6 mol/L). Cocaine alone produced no contractions, but increased the epinephrine sensitivity by 51% and the maximal response by 33%. When β-adrenoceptors were blocked with dl-propranolol (2 μmol/L), the contractile response to epinephrine was increased, and cocaine's effect was blocked. In the presence of the stereoisomer d-propranolol (2 μmol/L) with no β-adrenergic antagonist activity, the contractile response to epinephrine was unchanged, but the effect of cocaine was still blocked. We conclude that cocaine directly augments the α-adrenergic contractile response of the pregnant rabbit uterus by a mechanism that is blocked by the non-β-adrenergic effects of propranolol. © 1991.