Dopamine terminals in the hippocampus and prefrontal cortex modulate cognitive processes such as spatial learning and working memory. Because dopamine D4 receptors are expressed in these brain areas we have analyzed mutant mice lacking this receptor subtype (D rd4 -/-). Wild-type and D rd4 -/- mice were challenged in two spatial learning paradigms: the Morris water maze and an alternation T-maze. D rd4 -/- mice showed normal place learning ability to find a hidden platform based on spatial extra-maze cues. In addition, Drd4 -/- mice were able to find a new platform location with the same learning plasticity as wild type-mice. Spatial working memory assessed on a T maze showed that Drd4 -/- mice were more efficient than wild-type mice in acquiring the maximum plateau of correct alternation scores. These results provide further evidence that the functional consequence of lacking D4 receptors is more evident in behaviors dependent on the integrity of the prefrontal cortex.