Several neurotoxins have been isolated from bee venom. One of these, the mast cell degranulating peptide (MCD), releases histamine from mast cells and on central administration produces arousal at low concentrations and convulsions at higher doses. These effects are mediated through specific high-affinity binding sites which are concentrated in cortical structures, notably the hippocampus. This structure appears to be the source of changes in the electrocorticogram that follow injections of MCD into the cerebral ventricle, and which induce a quasi-permanent hippocampal theta rhythm in the motionless rat alternating with epileptiform spike waves. We report here that brief application of MCD to the CA1 region of hippocampal slices induces long-term potentiation, that is, a long-lasting increase in the efficacy of synaptic transmission. This potentiation seems to be indistinguishable from the classical LTP produced by trains of high-frequency electrical stimulation and considered to be related in some way to memory. Using binding to synaptosomal membranes and radioimmunoassay techniques, we have also found an endogenous peptide equivalent of MCD in brain extracts. This raises the possibility that a MCD-like peptide may be important in long-term potentiation.