This study investigated whether exposure to cocaine during critical periods of brain development alters the motor stimulating effects of amphetamine given in adulthood. Female rats received 50 mg/kg/day cocaine HCl SC or vehicle during either postnatal days 1-10 or 11-20. At 60-65 days of age, activity counts were collected over a 15-min baseline period. Subjects then received one of 3 doses (0, 0.1, 0.25 mg/kg) of d-amphetamine sulfate SC followed by a 90-min period of activity monitoring. Adult activity in 1-10-day cocaine-treated rats was different from vehicle-treated rats in response to 0.1 mg/kg amphetamine only. Adult activity in 11-20-day cocaine-treated rats was different from vehicle-treated rats in response to 0.25 mg/kg only. The observed differences represented an increase and decrease in activity, respectively. These alterations in amphetamine response may be related to the observed alterations in D-1 receptor concentrations as well as the altered rates of brain glucose metabolism we have observed in adult rats neonatally exposed to cocaine.