During a preexposure period rats were injected once daily with either cocaine HCI (10 mg/kg, IP) or the saline vehicle for 12 consecutive days. Rats that were chronically exposed to cocaine during the pretreatment phase were more responsive to the motor activating effects of a subsequent injection of cocaine than were rats chronically treated with saline. In self-administration testing, saline-pretreated groups did not exhibit a significant preference for a lever producing a cocaine infusion relative to an inactive lever, suggesting that the doses tested (0.225 and 0.45 mg/kg/infusion) were subthreshold for cocaine reward. In contrast, subjects preexposed to cocaine had a higher rate of reinforced responses and exhibited a preference for a lever that resulted in a cocaine infusion. It was unlikely that the higher response rate was due to an elevation in nonspecific activity since inactive lever responding remained low and relatively invariant over the 9 days of testing. Thus the enhanced responding in the cocaine-preexposed rats suggests that the reinforcing effectiveness of the drug had increased. These data indicate that sensitivity to cocaine's behavioral effects can be enhanced and that predisposing factors to cocaine abuse can be manipulated.