Dopamine is equally well deaminated oxidatively by monoamine oxidase (MAO) A and B types. Selegiline (L-deprenyl), a selective inhibitor of MAO-B, ameliorates the "wearing off" akinesia and delays the need for levodopa in mild, previously untreated Parkinson's disease. The therapeutic potential of selective inhibition of MAO-A in Parkinson's disease has not been examined in detail. MAO-A accounts for only about 20% of total MAO activity in the human basal ganglia, and it differs from MAO-B in distribution. In contrast to MAO-B, which is confined to the extraneuronal compartment, MAO-A is found both extraneuronally and within the presynaptic dopaminergic terminals. The inhibition of MAO-A might alter the intraneuronal handling of dopamine reuptaken from synaptic clefts and thereby prolong oral levodopa benefit. We have given moclobemide, a selective, reversible inhibitor of MAO-A, to nondepressed patients with Parkinson's disease receiving standard levodopa/peripheral decarboxylase inhibitor or levodopa with dopaminergic agonist (bromocriptine, pergolide). Selegiline was discontinued at least 8 weeks earlier. A standard oral levodopa challenge was performed at the patient's entry to the study and repeated on the 22nd day of moclobemide treatment (150 mg thrice daily). The overall time spent "on" and "off" before the onset of treatment and during the last week on the drug was estimated from the patients' diaries. Neuropsychological assessments were also made before and after 3 weeks of moclobemide to measure possible effects on cognitive performance and mood. In acute levodopa challenge, the latency of motor response was significantly shortened and its duration was prolonged during moclobemide treatment.(ABSTRACT TRUNCATED AT 250 WORDS)