The dopamine D(1) receptor is considered to participate in levodopa's antiparkinsonian action and levodopa-induced dyskinesias. We examined the functional status of the D(1) receptor in brain of patients with Parkinson's disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Dopamine-stimulated adenylyl cyclase activity was significantly increased in putamen (+43%) and frontal cortex (+52%) in PD, normal in PSP, but decreased by 47% in putamen in MSA. The supersensitive dopamine D(1) receptors in both striatum and cerebral cortex in PD might compensate for dopamine deficiency, but could also contribute to long-term complications of levodopa therapy.