Extensive research has shown that the hippocampus is necessary for consolidation of long-term spatial memory in rodents. We reported previously that rats using a place strategy to solve a cross maze task showed sustained phosphorylation of hippocampus cyclic AMP response element-binding protein (CREB), a transcription factor implicated in long-term memory formation. In the current study, we used viral vector-mediated gene transfer to test the hypothesis that formation of long-term memory for place learning can be facilitated by increasing levels of CREB in the dorsal hippocampus. Three days after intrahippocampus infusion, experimental (HSV-CREB) and control (HSV-LacZ; saline) rats were trained during a single session on a place task in a water cross maze. Rats were tested for memory 5 d later. Rats in all groups showed short-term memory, and there were no significant differences among treatment groups during acquisition. However, only HSV-CREB-infused rats showed significant savings between training and test, while HSV-LacZ- and saline-treated rats did not. Quantitative Western blotting confirmed that levels of dorsal hippocampus CREB were increased during training in rats infused with HSV-CREB in comparisons with controls. The present results show that formation of long-term memory can be facilitated by increasing levels of hippocampus CREB protein.