In Hydra, the transcription factor CREB is rapidly phosphorylated after amputation in the endodermal cells of the head-regenerating tips, a regulation that plays an important role in the head regeneration process. In bilaterians, the phosphorylated form of CREB binds to the CREB binding protein (CBP), which acts as a general co-activator of transcription. To find out if this regulatory cascade also occurs in Hydra, we analyzed the Hydra CBP protein which we found to be highly conserved during evolution. We detected a high level of CBP transcripts in the endodermal cells of the head-forming regions, either head-regeneration tips or buds growing from intact animals. We also noted hyper-acetylation of histone-4 in head-regenerating tips, and a marked negative effect of Scriptaid, a deacetylase inhibitory drug, on the efficacy of head regeneration. These preliminary results suggest that Hydra CBP could, via chromatin modifications, participate in the reactivation of the head re-development program.