In this experiment, rats were administered nicotine (0.3 mg/kg) for 11 consecutive days before and after an electrolytic medial frontal cortex lesion. After drug administration ceased, rats were tested on two spatial memory tasks, the radial arm maze (RAM) and the Morris water task (MWT). Behavioral testing was arranged so that rats were tested on the RAM 1 day after drug administration followed by behavioral testing on the MWT 19 days after drug treatment, or tested on the MWT 1 day after drug administration followed by testing on the RAM 4 days after drug treatment. Results of MWT testing showed that regardless of the drug/behavioral testing interval, lesioned rats given nicotine demonstrated enhancement relative to saline-treated lesioned animals, but the effects were more robust 1 day after drug treatment had ceased. Nicotine-induced behavioral compensation after medial frontal cortex lesions appears to be time-dependent in animals behaviorally tested on the MWT. Results of RAM testing showed that there were no significant differences between lesioned groups at the 1-day drug/testing interval, although nicotine improved performance in non-lesioned rats compared to non-lesioned rats given saline. Four days after drug administration, nicotine improved performance in lesioned rats to the levels of non-lesioned rats given saline or nicotine. This result suggests that previous training on the MWT may have primed behavioral compensation produced by nicotine in medial frontal cortex lesioned rats behaviorally tested on the RAM.