LONG-term potentiation (LTP) refers to a persisting enhancement of neurotransmission that follows high-frequency activation of certain synapses¹. Although both pre- and postsynaptic mechanisms contribute to LTP^2,3, it is believed that the enhanced release of neurotransmitter that accompanies this process results from the production of a diffusible messenger in postsynaptic neurons which traverses the synaptic cleft and alters the function of presynaptic terminals^4,5. One candidate for such a messenger is arachidonic acid, a metabolite produced by phospholipase A₂ which augments synaptic transmission when coupled with presynaptic stimulation⁵. However, the effects of arachidonic acid require activation of the postsynaptic receptor for N-methyl-D-aspartate⁶. Previously we found that platelet-activating factor (1 O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), another phospholipase A₂-derived messenger⁷, selectively enhances excitatory postsynaptic currents in hippocampal neurons by a presynaptic mechanism⁸. We now present evidence that platelet-activating factor, acting at a receptor localized to synaptic regions, participates in LTP in the CA1 region of rat hippocampal slices and may serve as part of a retrograde signalling cascade..