Several environmental neurotoxins and oxidative stress inducers are known to damage the nervous system and are considered major factors associated with the selective vulnerability of nigral dopaminergic neurons in Parkinson's disease (PD). Gamma-glutamylethylamide (L-theanine), a natural glutamate analog in green tea, has been shown to exert strong anti-ischemic effect. In this study, we investigated the protective effects of L-theanine on neurotoxicity induced by PD-related neurotoxicants, rotenone and dieldrin in cultured human dopaminergic cell line, SH-SY5Y. Our initial experiments revealed that L-theanine (500 microM) attenuated both rotenone- and dieldrin-induced DNA fragmentation and apoptotic death in SH-SY5Y cells. In addition, L-theanine partially prevented both rotenone- and dieldrin-induced heme oxygenase-1 (HO-1) up-regulation. Both rotenone- and dieldrin-induced down-regulation of extracellular signal-regulated kinase1/2 (ERK1/2) phosphorylation was significantly blocked by pretreatment with L-theanine. Furthermore, pretreatment with L-theanine significantly attenuated the down-regulation of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) production in SH-SY5Y cells. These results suggest that L-theanine directly provide neuroprotection against PD-related neurotoxicants and may be clinically useful for preventing PD symptoms.