Moclobemide, a potent reversible monoamine-oxidase A (MAO-A) inhibitor, is an effective antidepressant that does not cause impairment of cognitive function in elderly patients and might be beneficial to motor deficits in Parkinson's disease (PD). In a 12-week open-label prospective study, we administered moclobemide (300-600 mg day(-1)) as an add-on medication to twelve PD patients who met DSM-III-R criteria for depressive illness. There were two early drop-outs due to subjective worsening of Parkinsonism associated with insomnia and anorexia, respectively. The Beck Depression Inventory score decreased significantly in the ten patients who completed the study, and clinical global assessment of efficacy recorded 'good' or 'excellent' responses or in nine of the ten patients. Mean parkinsonian disability, as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) and Schwab-England Daily Life Activities scales, remained unchanged throughout the study in the group as a whole. However, worsening or onset of resting tremor occurred in five patients and the UPDRS tremor subscore in the group overall was significantly higher by week 8 (p = 0.03) when dose titration was optimal. There was a trend toward improvement in UPDRS bradykinesia subscores that did not attain statistical significance. Compared to baseline, patients complained more often of insomnia, anorexia, increased perspiration, and restlessness. Though these preliminary results need to be replicated in a large controlled trial, we suggest that moclobemide may be an effective alternative in the treatment of PD associated depression.