Terguride (TER), a semisynthetic derivative of lisuride, has been found to display dopamine (DA) agonist and DA antagonist effects in animals, depending on the experimental model used. TER (2 mg/day) was compared to placebo in 41 fluctuating Parkinson's disease patients to test its effect on akinesia and dyskinesia. Mean hours “off” decreased at weeks 6 and 12 (p < 0.05) in the TER group but the overall difference from the placebo group was not significant. Only the TER group displayed a decrease over time in mean Columbia University Rating Scale total score “on” and “off” (p = 0.001 and p = 0.03, respectively). Duration of involuntary movements and resulting disability were not significantly different between patients on TER and those on placebo administration. In the overall evaluation, patients preferred TER (p = 0.01). Tolerance of TER was very good in all but one patient whose wearing-off increased; no one dropped out because of side effects. This 3-month doubleblind study showed that TER, added to stable doses of L-dopa, may have slight antiparkinsonian efficacy.