This study looked at the effects of neonatal cocaine exposure on activity rhythms over a 48-h period in rats. Subjects were artificially-reared from postnatal days (PN) 4-10 via intragastric cannulas. The four treatment groups included two cocaine doses (20 and 40 mg/kg per day), an artificially-reared control and a normally reared suckled control. Subjects were tested at PN 38-40 in an automated running wheel. Neonatal cocaine exposure did not alter activity rhythms over the 48-h test period. However, there was a gender-specific effect of neonatal cocaine exposure on response to the novel test chamber and to the experimenter. The 20 mg/kg cocaine-exposed females showed increased running wheel activity relative to all other groups after placement in the running wheel. During the second 24-h period, cocaine-exposed females from both cocaine groups showed increased activity relative to controls following the entry of an experimenter to the test room. These findings suggest that female rats exposed to cocaine neonatally show an increased response to novel environments and stimuli.