Chronic exposure to manganese causes parkinsonian symptoms and has been implicated as an environmental factor in the pathogenesis of Parkinson's disease (PD). Here we show that manganese inhibits the proliferation of PC12 cells and induces apoptosis through the formation of catechol isoquinolines. Manganese induces the production of 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol, Sal) and N-methyl-salsolinol (NMSal) in PC12 cells, and increases the levels of malondialdehyde (MDA) in a dose-dependent manner. The data indicates that the formation of catechol isoquinolines due to oxidative stress induced by MnCl(2) may be a mechanism by which manganese causes degeneration of dopaminergic neurons.