Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Some of the inherited forms of the disease are caused by mutations in the α-synuclein gene and the triplication of its locus. Oxidative stress has been proposed as a central mechanism for the progression of the disease although its relation with α-synuclein toxicity remains obscure. Targeted expression of human α-synuclein has been effectively used to recreate the pathology of PD in Drosophila melanogaster and it has been proved an excellent tool for the study of testable hypothesis in relation to the disease. We show that dopaminergic neurons are specifically sensitive to hyperoxia induced oxidative stress and that mutant forms of α-synuclein show an enhanced toxicity under these conditions suggesting synergic interactions. In addition, the co-expression of Cu/Zn superoxid dismutase protects against the dopaminergic neuronal loss induced by mutant α-synuclein overexpression thus identifying oxidative stress as an important causative factor in the pathology of autosomal-dominant Parkinsonism.