delta 1-Piperidine-2-carboxylic acid (P2C), an intermediate of the L-lysine metabolic pathway in the brain, was studied for its uptake and metabolism in the synaptosome of the rat cerebral cortex. The results of this study showed that the uptake of P2C into the synaptosome was NA+- and temperature-dependent with a two-tier transport kinetic (Km = 2.6 and 0.7 microM; Vmax = 1.6 and 0.73 pmol/min/mg). P2C uptake was only moderately inhibited (approximately 20%) by L-lysine and its metabolites, L-pipecolic acid and L-alpha-aminoadipic acid at up to 100 microM, and the putative amino acid neurotransmitters, gamma-aminobutyric acid, L-glutamic acid and L-aspartic acid (25-31%) at 5-500 microM. The synaptosomal preparation only has a very low activity for metabolizing P2C to its product L-pipecolic acid. The metabolic activity for P2C was mainly contained in the 27,000 x g supernatant S2 fraction. Since P2C is the precursor of the putative neuromodulator L-pipecolic acid, the understanding of its uptake and metabolic characteristics in the brain should be of significance.