The Deprenyl and Tocopherol Antioxidant Therapy of Parkinsonism (DATATOP) trial was designed to test outcomes from treatment with 10 mg of deprenyl and/or 2,000 mg of tocopherol/day in 800 untreated patients with Parkinson's disease. The need of subjects for symptomatic treatment with levodopa and the conversion of all subjects to open-label deprenyl made it possible to study the long-term effect of early deprenyl and tocopherol treatment on the later development of levodopa-associated side effects. The rate of developing these side effects did not differ among the original treatment groups (early versus late deprenyl and tocopherol versus nontocopherol). About 50% of subjects developed "wearing off," 30% dyskinesias, and 25% "freezing" in each group. At the end of the study, the groups were similarly disabled on the Hoehn-Yahr, Schwab-England, and Unified Parkinson's Disease Rating scales and took similar amounts of levodopa. Young subjects were more likely to develop wearing off, women to develop dyskinesias, and older subjects with rapidly progressive disease to develop freezing. We conclude that prior treatment with deprenyl or tocopherol did not reduce the occurrence of subsequent levodopa-associated adverse effects in this population.