The effects of acute levodopa withdrawal were studied in nine patients with levodopa related on-off oscillations. One patient withdrew from the study due to off period confusion and hallucinations. A marked deterioration in motor disability occurred in all patients following overnight withdrawal of levodopa and a further mild delayed deterioration was present over a mean withdrawal period of 44 hours. Patients with more severe disease were able to tolerate levodopa withdrawal for a shorter period of time than those with milder disease severity. The minimum therapeutic dose of subcutaneous apomorphine needed to produce a similar improvement in patients' mobility, before and after several days of drug withdrawal, did not differ, thus providing no clinical evidence for alterations in striatal dopamine receptor sensitivity after acute levodopa withdrawal.