OBJECTIVE: To study the reappearance of the clinical signs of PD when subthalamic nucleus (STN) deep brain stimulation (DBS) was turned off. METHOD: The authors studied 35 patients treated with STN DBS 6.7 +/- 3.3 months (mean +/- SD) after implantation. All were clinically improved. Twenty-four had not required any antiparkinsonian medication for many months and 11 were in "practically defined off" conditions when studied. Unified Parkinson's Disease Rating Scale (UPDRS) motor scores were assessed at baseline and 5, 15, 30, 60, 90, 120, 150, 180, and 240 minutes after switching off STN DBS. RESULTS: A sequential pattern of return of parkinsonian signs was observed, with a fast worsening of tremor within minutes, followed by a smoother, slower worsening of bradykinesia and rigidity over half an hour to an hour, and finally a slow and steady worsening of axial signs over 3 to 4 hours. Ninety percent of the UPDRS motor score worsening was reached after 2 hours. When switching STN DBS "on" again, all motor UPDRS subscores improved with a similar pattern, but faster than their rate of worsening, especially for axial signs. CONCLUSIONS: STN DBS may act by different mechanisms on the four major parkinsonian signs. At least 3 hours off STN DBS is needed to estimate the clinical effect of stimulation.