OBJECTIVE: To characterize the effect of cocaine on catecholamine uptake by myometrium from pregnant women. METHODS: Slices of myometrium obtained from nine women during elective cesarean delivery at term were incubated with [3H]-norepinephrine and various uptake inhibitors for 30 minutes. The radiolabeled material was extracted with perchloric acid, expressed as percent control (+/- standard error of the mean), and compared by one-factor analysis of variance and Fisher multiple range test. RESULTS: Myometrial uptake was inhibited by cocaine (42 +/- 9%) by neuronal (type 1) uptake inhibitors (desipramine 41 +/- 14%; N-ethylmaleimide 53 +/- 8%), and by extraneuronal (type 2) inhibitors (normetanephrine 56 +/- 19%; corticosterone 73 +/- 9%). When uptake inhibitors were used in combination with cocaine, uptake was not decreased further in the presence of neuronal inhibitors (desipramine plus cocaine 40 +/- 20%; N-ethylmaleimide plus cocaine 42 +/- 4%). However, the effect of cocaine appeared to be added to that of extraneuronal inhibitors (normetanephrine plus cocaine 25 +/- 14%; corticosterone plus cocaine 32 +/- 1%). CONCLUSION: Catecholamine uptake by myometrium in pregnant women appears to be both extraneuronal and neuronal in nature, and cocaine inhibits the neuronal portion of this uptake. This mechanism may play a role in the increased rate of premature delivery associated with cocaine abuse.