Long-term memory formation consists of multiple phases. A new memory is initially labile and sensitive to disruption by a variety of interfering events or agents. To become stable, this new memory undergoes a process known as consolidation, which, in the case of declarative memories, occurs within the medial temporal lobes and requires gene expression. When recalled, memories re-enter a new phase of vulnerability and seem to require a reconsolidation process in order to be maintained. Here we show that consolidation but not reconsolidation of inhibitory avoidance memory requires the expression of the transcription factor CCAAT enhancer binding protein (C/EBP) in the hippocampus. Furthermore, in the same region, de novo protein synthesis is not essential for memory reconsolidation. C/EBP is an evolutionarily conserved genetic marker that has a selective role in the consolidation of new but not reactivated memories in the hippocampus.