Tolcapone, a catechol-O-methyltransferase inhibitor, can interfere with the metabolism of levodopa and dopamine and could prolong the motor effect induced by levodopa in parkinsonian patients. To test this hypothesis, we studied the motor effect induced by three acute administrations of a dose of levodopa-benserazide (Madopar) with either 200 mg or 400 mg of tolcapone or placebo, in a double-blind latin-square design. The duration of the on-phase could be compared in 10 parkinsonian patients suffering from square-shaped motor effect. In comparison to placebo, 200 mg and 400 mg of tolcapone significantly increased the mean duration of the on-phase by 61.7 min ( +/- 19.4 SEM) and by 72.2 min ( +/- 18.5), respectively. This clinical effect is suggested to be related mainly to the increase in levodopa area under the curve and half-life induced by tolcapone. The intensity in dyskinesias was increased by 400 mg of tolcapone. Tolcapone appears to be well tolerated and could be helpful as an adjuvant treatment to levodopa in parkinsonian patients with motor fluctuations.