Animal studies have demonstrated potent antiparkinsonian and other motor effects of the functional NMDA-antagonist flupirtine and suggest a therapeutic use in Parkinson's disease (PD). In healthy subjects flupirtine decreases the functionally destabilizing medium latency (ML) response following toe-up rotations of a moving platform. Because ML responses are known to be increased in PD, this study examined s the effects of flupirtine on postural responses in patients with PD. During 22 days 21 patients with PD took 50 mg, 100 mg flupirtine or placebo following a randomized, double-blind design. Clinical impairment was assessed by means of the Unified Parkinson's Disease Rating Scale (UPDRS). No significant difference between the effect of flupirtine and placebo on ML responses was observed. There was an unspecific improvement of overall UPDRS scores in placebo and flupirtine conditions compared with baseline measures which was more marked in the placebo condition. No improvement in the UPDRS motor subscale was observed. As no beneficial effect on the clinical presentation and no effect on postural responses could be demonstrated, flupirtine does not seem to be a therapeutic option in PD.