We investigated the role of acyl-CoAs during induction and maintenance of long-term potentiation in rat brain hippocampus. Changes of acyl-CoA and free fatty acids (FFA) in hippocampus were measured during tetraethylammonium (TEA)-induced LTP, Results indicated that concentrations of acyl-CoAs and FFAs in slices were changed during TEA-induced LTP and 16:0-CoA and 18:0-CoA were increased in the early phase of stimulation, whereas free fatty acids in this phase were rather decreased. The increase of 20:4-CoA was delayed more than saturated acyl-CoAs, To examine the role of acyl-CoA in LTP of evoked transmitter release, we measured the glutamate release from hippocampal slice with the addition of acyl-CoA using glutamate electrode. Acyl-CoA (16:0-, 18:1-, and 20:4-CoA) could enhance glutamate release in hippocampal slice. It is suggested that saturated acyl-CoAs may play a functional role in the early phase of LTP,