Previously, we proposed that S-nitroso-l-cysteine, an endogenous S-nitrosothiol, was incorporated via the system L-like amino acid transporter(s) in rat brain slices. In this study, we investigated the effect of S-nitroso-l-cysteine on l-[ 3 H]leucine uptake in PC12 cells (a neuronal cell line). l-[ 3 H]Leucine uptake in PC12 cells was Na + independent and significantly inhibited by an inhibitor of system L and by l-phenylalanine, l-cysteine, l-methionine and l-leucine at 1 mM. The effects of l-alanine, l-serine and l-threonine were limited. S-Nitroso-l-cysteine, but not other nitric oxide compounds, inhibited l-[ 3 H]leucine uptake, and this inhibitory effect was eliminated by washing with buffer. System L is composed of the 4F2 light chains (LAT1 or LAT2) and the heavy chain, and the transcripts of these components were detected in RNA from PC12 cells. These findings suggest that S-nitroso-l-cysteine is incorporated via the system L amino acid transporter and thus regulates cell responses in PC12 cells.