Activation of the transcription factor CREB is thought to be important in the formation of long-term memory in several animal species [1-3]. The phosphorylation of a serine residue at position 133 of CREB is critical for activation of CREB . This phosphorylation is rapid when driven by brief synaptic activity in hippocampal neurons . It is initiated by a highly local, rise in calcium ion concentration  near the cell membrane, but culminates in the activation of a specific calmodulin-dependent kinase known as CaMK IV , which is constitutively present in the neuronal nucleus [7,8]. It is unclear how the signal is conveyed from the synapse to the nucleus. We show here that brief bursts of activity cause a swift ([approximately] 1 min) translocation of calmodulin from the cytoplasm to the nucleus, and that this translocation is important for the rapid phosphorylation of CREB. Certain Ca2+ entry systems (L-type Ca2+ channels and NMDA receptors) are able to cause mobilization of calmodulin, whereas others (N- and P/Q-type Ca2+ channels) are not. This translocation of calmodulin provides a form of cellular communication that combines the specificity of local Ca2+ signalling with the ability to produce action at a distance.