Kessler, 1.1. (Johns Hopkins Univ. School of Hygiene and Public Health, Baltimore, Md. 21205) and E. L. Diamond. Epidemiologic studies of Parkinson's disease. I. Smoking and Parkinson's disease: a survey and explanatory hypothesis. Amer J Epidem 94: 16–25, 1971.—Nicotine has long been known to affect the central and peripheral nervous systems of man. It has variously been regarded as an exacerbating factor or as a therapeutic modality in Parkinson's disease. Three prospective studies have demonstrated a lower risk of death from Parkinson's disease among smokers than nonsmokers. A previous retrospective study confirmed that patients with this condition are less likely to smoke tobacco than other patients, but attributed this to an artifact resulting in the selection of control patients with excessive smoking habits. In the present investigation, the smoking histories of all Baltimore residents discharged with a diagnosis of Parkinson's disease from the hospitals of Baltimore over a 2-year period were ascertained. These patients were less likely to have ever smoked and, if smokers, tended to smoke less than a comparable group of patients without Parkinson's disease. Tremors, rigidity, hypokinesia and alterations in facies and speech were somewhat less prevalent among male parkinsonians who smoked than among those who did not. Relatively few female patients smoked and these did not differ substantially in their neuropathologic symptoms from the nonsmokers. Smokers tended to develop neurologic deficits at an earlier age than nonsmokers, thus suggesting the possibility of two forms of Parkinson's disease—one more refractory than the other to the effects of nicotine. An hypothesis involving known metabolic pathways of the biogenic amines is suggested for further study of the observed relationships between smoking and Parkinson's disease.