Parkinson's disease is a neurodegenerative disease whose hallmark pathological features include a selective loss of dopaminergic neurons in the midbrain. Ciclooxygenase-2 activity induction and oxidative stress have been implicated in the aetiology of Parkinson's disease and in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model of Parkinson disease. Upon administration of fish oil, melatonin and vitamin E, neuroprotective effects on MPTP-induced neurotoxicity have been indicated. The aim of this study was to investigate the time course and compare the potency of these agents alone, on several parameters such as COX-2 and lipid peroxides (LPO) products associated with MPTP neurotoxicity in midbrain homogenates of C57BL/6 mice. Using fish oil (0.0368 g EPA and 0.0184 g DHA, per day), melatonin (10 mg/kg/day), and vitamin E (50 mg/Kg/day) we have now shown that COX-2 activity, LPO and nitrite/nitrate levels were significantly increased in MPTP treated mice (p