This study investigates the association between exposure to pesticides and Parkinson's disease (PD) in humans. The researchers used a case-control design nested within the Agricultural Health Study (AHS), which included pesticide applicators and their spouses. They assessed lifetime pesticide use and diagnosed PD through in-person evaluations by movement disorders specialists. The study found that PD was positively associated with exposure to pesticides that inhibit mitochondrial complex I, such as rotenone, and those that cause oxidative stress, such as paraquat. Specifically, the odds ratios (ORs) for PD were 1.7 (95% CI, 1.0–2.8) for complex I inhibitors and 2.0 (95% CI, 1.2–3.6) for oxidative stressors. These findings support the role of mitochondrial dysfunction and oxidative stress in the pathophysiology of PD. The study also highlights the potential public health significance of these pesticides, given their widespread use.This study investigates the association between exposure to pesticides and Parkinson's disease (PD) in humans. The researchers used a case-control design nested within the Agricultural Health Study (AHS), which included pesticide applicators and their spouses. They assessed lifetime pesticide use and diagnosed PD through in-person evaluations by movement disorders specialists. The study found that PD was positively associated with exposure to pesticides that inhibit mitochondrial complex I, such as rotenone, and those that cause oxidative stress, such as paraquat. Specifically, the odds ratios (ORs) for PD were 1.7 (95% CI, 1.0–2.8) for complex I inhibitors and 2.0 (95% CI, 1.2–3.6) for oxidative stressors. These findings support the role of mitochondrial dysfunction and oxidative stress in the pathophysiology of PD. The study also highlights the potential public health significance of these pesticides, given their widespread use.