Parkinson's disease results in part from the loss of dopamine neurons. We hypothesize that exercise reduces the vulnerability of dopamine neurons to neurotoxin exposure, which is modulated by stress. We have outlined experiments to test this hypothesis in rats treated with one of several neurotoxins, beginning with 6-hydroxydopamine. Over the past year, we increased the size and training of our research team and made a number of observations of direct relevance to our hypothesis. We also have received permission to expand our original Statement of Work to include critical studies on the mechanism of the actions of exercise, using both in vivo and in vitro approaches. Our focus continues to be on the effects of stress and exercise on the vulnerability of DA neurons, and the role played in these phenomena by trophic factors and intracellular signaling cascades.