Rats bearing electrolytic lesions of medial septum and sham-operated controls were trained on cocaine place-preference in a 3-compartment apparatus. Cocaine was paired with a white or a black compartment. An unbiased design was used, in which cocaine was paired with the preferred side in half the animals and with the unpreferred side in the other half. Two low doses of cocaine HCl were used: 2.5 and 5.0 mg/kg. Only two pairings of drug with environment were used to minimize the influence of drug sensitization. Rats with septal lesions, but not controls, showed preference conditioning to the black side at 2.5 mg/kg; lesioned and control animals showed similar conditioning to the black side at 5.0 mg/kg. Lesioned animals could not be conditioned to the white side at either dose. This was attributed to a drug-induced enhancement of a previously described increased reactivity to brightness following septal lesions. Controls conditioned to either side at 5.0 mg/kg. It was concluded that septal lesions lowered the cocaine dose required for preference conditioning, consistent with reports that such damage enhances some behavioral effects of psychostimulants.