This study is concerned with the question whether the medial prefrontal cortex mediates spatial navigation requiring the expression of response learning. It consists of two parts. In the first experiment it was investigated whether intact male Wistar rats can learn a spatial response task in a Morris water maze, and, if so, how the learning of this task compares with the learning of a place task, in the same water maze. The data illustrate that rats can indeed learn the response task demands, but also demonstrate that this task is more difficult to learn than the place task. This is evidenced by a slower and more capricious acquisition. Based on these findings a second experiment was conducted, in which sham-operated rats and rats with damage of the medial prefrontal cortex (mPFC) were compared for their acquisition in the response task in the Morris water maze. The results showed that both escape latency and path length of the mPFC-damaged animals were significantly higher than those of the sham-operated animals. A behavioral analysis of the swimming paths demonstrated that the mPFC-damaged rats were more persistent in their use of a place strategy, while the sham-operated animals sooner switched to the more successful taxon-orientation strategy. Taken together with previous findings these data support the hypothesis of a functional dissociation of the mPFC with regard to its involvement in the expression of place and response learning.