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Previous studies based on limited exposure assessment have suggested that Parkinson's disease (PD) is associated with pesticide exposure. The authors used data obtained from licensed private pesticide applicators and spouses participating in the Agricultural Health Study to evaluate the relation of self-reported PD to pesticide exposure. Cohort members, who were enrolled in 1993–1997, provided detailed information on lifetime pesticide use. At follow-up in 1999–2003, 68% of the cohort was interviewed. Cases were defined as participants who reported physician-diagnosed PD at enrollment (prevalent cases, n=83) or follow-up (incident cases, n=78). Cases were compared with cohort members who did not report PD (n=79,557 at enrollment and n=55,931 at follow-up). Incident PD was associated with cumulative days of pesticide use at enrollment (for highest quartile vs. lowest, odds ratio (OR)=2.3, 95% confidence interval: 1.2, 4.5; p-trend=0.009), with personally applying pesticides more than half the time (OR=1.9, 95% confidence interval: 0.7, 4.7), and with some specific pesticides (ORs ≥ 1.4). Prevalent PD was not associated with overall pesticide use. This study suggests that exposure to certain pesticides may increase PD risk. Findings for specific chemicals may provide fruitful leads for further investigation.