The effect of piperidine and D, L-pipecolic acid on a Ca2+-dependent release of L-[3H]noradrenaline (L-[3H]NA), [3H]5-hydroxytryptamine ([3H]5-HT) and [14C]GABA from the rat brain slices preloaded of radioactive amines and acid were investigated. Piperidine 10-4M did not affect high K+-induced release of L-[3H]NA, [3H]5-HT and [14C]GABA as well as spontaneous release of these amines and acid. On the other hand, D, L-pipecolic acid (10-4m) significantly increased high K+-induced release of [14C]GABA but not of L-[3H]NA or [3H]5-HT. These results suggest that the hypnogenic and tranquilizing effect of piperidine is due to other mechanism than influence on NA, 5 HT and GABA at nerve terminals of central NA, 5 HT and GABA neurons, and that pipecolic acid possibly could potentiate the synaptic transmission of GABA in the central nervous system. © 1979, The Pharmaceutical Society of Japan. All rights reserved.