Cabergoline, a new ergoline derivative with potent and long-lasting dopaminergic activity, is a promising drug for overcoming the akinetic episodes in L-Dopa-treated Parkinson's disease patients with motor fluctuations. Its long plasma half-life (65 h) allows a single daily dose administration. Seventeen patients with Parkinson's disease (mean age 66 years; mean disease duration 8.8 years; median Hoehn and Yahr stage, III) were included in an open-label study. All had persistent motor fluctuations while treated with L-Dopa plus carbidopa (mean dose, 660 mg + 66 mg). Cabergoline was added until a maximal dose was achieved (5 mg daily), while L-Dopa was slightly diminished. Eight patients completed 1 year of treatment. They showed significant improvement in their motor performance (Unified Parkinson's Disease Rating Scale) (bradykinesia score decreased from 8.2 to 4.2, p < 0.005), and in the proportion of “off” time spent during waking hours (32–23%, p < 0.05). Three patients abandoned the trial because of increasing severity of dyskinesias, hallucinations, and depression (one each), six were withdrawn because of poor compliance and refusal to continue the treatment. This study suggests that cabergoline may play an important role in the treatment of Parkinson's disease with motor fluctuations.