Forty patients affected by severe Parkinson’s disease (PD) were treated with tolcapone as an adjunctive therapy to L-DOPA, for 3–7 months, until this drug was discontinued because of side-effects (2 diarrhoea, one of them with orthostatic hypotension, 2 increments of liver enzymes) or because of mandatory indications of the European drugs authority. All patients, after 3–6 months of L-DOPA therapy adjustments, received entacapone for 3 months again followed by withdrawal. L-DOPA daily dosage was significantly reduced by tolcapone and entacapone (p= 0.01 and 0.05).‘On’time was increased by 15% during tolcapone treatment (p< 0.05), and by 8% during entacapone treatment.‘Off’time was decreased by 16% during tolcapone and by 7% during entacapone treatment. Entacapone was withdrawn in the same patient who experienced diarrhoea and orthostatic hypotension during tolcapone because of recurrence of side-effects, in 6 patients because of increment of dyskinesias (with hallucinations) and in 1 patients because of rhythmic, jerking myoclonus.