Although the exact cause of Parkinson's disease is unknown, the results of animal experiments and postmortem studies among individuals with Parkinson's disease suggest that inflammation may contribute to the deaths of dopaminergic neurons. This hypothesis is supported by the observation that non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin and other common over the counter drugs, protect dopaminergic neurons in animal models of Parkinson's disease. In a preliminary study we found that individuals who regularly took NSAIDs had a 45% lower risk of Parkinson's disease than those who never used these drugs. This result is intriguing, but it needs to be confirmed in a larger population. We therefore propose to identify individuals who developed Parkinson's disease among participants in a well-established prospective study, the Cancer Prevention Study II Nutrition Cohort (CPS-II). This study, comprising approximately160,000 men and women in the United States, is being conducted by the American Cancer Society to identify the causes of cancer. In 1992, participants were asked to report whether or not they used aspirin, acetaminophen, or other non-steroidal analgesics; users were asked to report the frequency, dosage, and duration of use for each drug. Participants were then followed from 1992 to 2001, updating the information on use of NSAIDs every two years. By identifying those members of this cohort who were diagnosed with Parkinson's disease during the follow-up, we will be able to address the following questions: 1) Do users of aspirin, other non-aspirin NSAIDs, or acetaminophen have lower risks of Parkinson's disease compared with non-users? 2) What is the dose-response relationship between use of these drugs and risk of Parkinson's disease? 3) How does the duration of NSAID use relate to risk of Parkinson's disease? Confirmation of our preliminary findings would provide strong evidence that use of NSAIDs may contribute to prevent Parkinson's disease. Further, these results would also suggest that regular use of NSAIDs could also benefit people with Parkinson's disease by slowing the neurodegenerative process.