Long-term potentiation has been involved in certain forms of learning and memory. In the CA1 region of the hippocampus, long-term potentiation (LTP) is triggered postsinaptically and, at least in part, it expression depends on presynaptic mechanisms. Therefore, a retrograde messenger that is released from the postsynaptic dendrite and diffuses back across the synapse to increase neurotransmitter release has been proposed. Several candidates including lipid mediators such as arachidonic acid and platelet-activating factor, and gases such as nitric oxide and carbon monoxide, have recently attracted much interest. The involvement of these intercellular messengers in LTP, the relation between LTP and memory and the role of these candidate retrograde messengers in the acquisition and consolidation of memories are discussed. Evidence for the involvement of NO, CO and PAF in the early stages of memory processing will be presented.