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Free cytoplasmic dopamine may be involved in the genesis of neuronal degeneration in Parkinson's disease and other such diseases. We used SH‐SY5Y human neuroblastoma cells to study the effect of dopamine on cell death, activation of stress‐induced pathways, and expression of α‐synuclein, the characteristic protein accumulated in Lewy bodies. We show that 100 and 500 μM dopamine causes a 40% and 60% decrease of viability, respectively, and triggers autophagy after 24 hr of exposure, characterized by the presence of numerous cytoplasmic vacuoles with inclusions. Dopamine causes mitochondrial aggregation in adherent cells prior to the loss of functionality. Plasma membrane and nucleus also maintain their integrity. Cell viability is protected by the dopamine transporter blocker nomifensine and the antioxidants N‐acetylcysteine and ascorbic acid. Dopamine activates the stress‐response kinases …