Parkinson's disease results from a progressive loss of dopaminergic neurones of the substantia nigra (SNc). Clinical symptoms only appear, however, when neuronal death exceeds 50-60%: their late appearance is due to compensatory mechanisms. The possibility exists that glutamatergic inputs to the SNc may be implicated in this 'masking' of the disease. To test this hypothesis, we evaluated the effects of reversible pharmacological blockage of these inputs in asymptomatic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. The result was the appearance of motor disturbances. This finding supports the idea that SNc glutamatergic inputs are largely involved in compensatory mechanisms during presymptomatic period. Blockade of these inputs could lead to presymptomatic diagnosis of Parkinson's disease.