Parkinson's disease is a neurodegenerative disorder associated with cell loss from the substantia nigra pars compacta (SNc). The dopaminergic cells of the SNc project to the striatum where the loss of dopaminergic tone is thought to be the main cause of Parkinsonism symptoms. Animal models have shown that striatal tissue content of dopamine declines proportionally to cell death in the SNc but the extracellular concentration of dopamine (EDA) in the striatum remains near normal until more than 85% of SNc neurons have died. We investigate various explanations for the remarkable homeostasis of EDA with a mathematical model that has recently been constructed for dopamine synthesis, release, and reuptake, which includes the effects of the autoreceptors. We provide evidence and explanations for the passive stabilization hypothesis and show that the autoreceptors enhance stabilization of EDA only when fewer than 25% of the SNc cells remain. © 2009 Elsevier Ltd. All rights reserved.