S-sulfo-cysteine (SSC) is an agonist of glutamate receptors which could be involved in cysteine-induced neurotoxicity. Here we analyzed SSC by HPLC and demonstrated that the concentration of SSC in cortex of cysteine-injected rats increased to 1.4 microM, about four times the value of control rats. The neurotoxic effect of SSC was evaluated in slice cultures of rat hippocampus and compared to NMDA and cysteine. The neurotoxicity threshold of SSC was well above the tissue concentration. Our results show that SSC increases in neonatal rat brain after cysteine injection but reaches a tissue concentration far below concentrations that induce neurotoxicity in vitro. Thus, even if all the tissue SSC after cysteine injection was extracellular it would be below the threshold for toxicity, indicating that SSC is not a main excitotoxin involved in cysteine toxicity.