Abstract: The effect of melatonin, a potent free radical scavenger, on L-cysteine-induced seizures and lipid peroxidation was investigated in mice. When L-cysteine (1.25, or 5.0 μmol/animal) was injected intracerebroventricularly (i.c.v.) into mice, severe tonic seizures were observed for over 20 sec in 75% and 100% of the treated mice, respectively. However, when melatonin (20 or 100 mg/kg) was injected subcutaneously (sc) into mice 15 min before L-cysteine injection (1.25 umol/animal, i.c.v.), the incidence of seizures was observed in only 35% and 20% of the treated mice, respectively. Furthermore, when L-cysteine (1.25 or 5.0 (amol/animal, i.c.v.) was injected into mice, lipid peroxidation in whole brain 20 min after injection was significantly increased by 56% or 67% as compared to that of the control. However, when the seizures induced by L-cysteine (1.25 μmol/animal) were abolished by preadminstration of melatonin, the increased lipid peroxidation induced by L-cysteine was prevented. These results suggest that there may be a positive correlation between free radical formation and seizures induced by L-cysteine and that melatonin affords protection against the seizures as well as against the associated lipid peroxidation.