After unilateral entorhinal cortex lesion, deficits on a working spatial memory Morris water maze task were examined in male and female rats to determine if gender differences exist in response to hippocampal deafferentation. Brain-damaged males showed a persistent water maze deficit that persisted throughout the 10 days of testing. Brain-damaged females did not. The performance of the injured females was only slightly impaired relative to sham males and females, and was significantly better than males with EC damage. This lack of a water maze deficit in lesion females is hypothesized to be due either to gender differences in sprouting responses or to a more flexible use of multiple cues by females relative to males.