The existence of the nigrofrontal dopaminergic pathway has been demonstrated in neuroanatomical studies. We evaluated the presynaptic nigrofrontal dopaminergic function using 18F-dopa (FD) positron emission tomography (PET). The multiple time PET data in the frontal cortex from 20 to 70 min post-injection for FD were evaluated by Patlak analysis using the cerebellar time-activity curve as an input function. The frontal FD uptake rate constants could not be determined in 5 of 12 normal volunteers because of large deviations in the plots. There were no significant differences between the subjects among whom the frontal FD uptake rate constants could or could not be determined regarding the amount of FD injected, the frontal 18F counts, or whether or not they were pretreated with carbidopa. The uptake constants were determined in 9 or 12 patients with parkinsonian syndrome. While the mean (+/- S.D.) uptake constants in patients with Parkinson's disease (2.89 +/- 0.06 x 10(-3), n = 4) and in patients with progressive supranuclear palsy (2.81 +/- 0.10 x 10(-3), n = 3) were not significantly different from those in the normal volunteers (2.93 +/- 0.14 x 10(-3)), those in two patients with corticobasal degeneration (2.42 and 2.46, respectively) decreased in comparison to the control values. Differences in the nigrofrontal presynaptic dopaminergic function as assessed by FD-PET may explain the different pathogenesis and also help to differentiate between corticobasal degeneration and other parkinsonian syndromes, such as Parkinson's disease and progressive supranuclear palsy.