Previous studies have shown an inverse association between smoking and the prevalence of Parkinson's disease (PD), suggesting that smoking may induce a biological protection against nigral neuronal damage. In 1993, we examined the frequency of cigarette smokers among 239 patients with PD and two control groups. In addition, the progression of parkinsonism and other clinical features were followed prospectively in smoking and nonsmoking PD patients over an 8-year period. Mortality in the two PD groups was also examined. We found a 50% higher prevalence of smokers in the control groups than in patients with PD. In contrast, during the follow-up period, there were no significant differences in progression of parkinsonism, cognitive impairment, and mood in smoking and nonsmoking patients with PD. Mortality was also similar in the two groups. The lack of influence on disease progression may indicate that cigarette smoking does not have a major neuroprotective effect in patients with already diagnosed PD.