In the course of their disease certain patients with frontotemporal dementia (FTD) develop clinical features compatible with a motor neuron disease (FTD-MND). Previous reports have suggested that the functional pattern is similar in FTD and FTD-MND. However, some neuropathological studies suggest greater involvement of medial temporal regions in FTD-MND than in FTD. Using statistical parametric mapping (SPM96), we compared the metabolic patterns obtained at rest with positron emission tomography in 10 FTD patients and three FTD-MND patients with those obtained from 46 healthy subjects (HS). Mean age, duration of illness and dementia stage did not differ statistically between the FTD and FTD-MND groups. In comparison with HS, both groups showed frontal and anterior temporal hypometabolism at P<0.001. When the FTD-MND group was compared to the FTD group, significant hypometabolism was only observed in bilateral amygdala, bilateral hippocampus, and bilateral enthorinal and parahippocampal regions (Brodmann's areas, BA 28/36) at P<0.005. We found no significant differences in regional glucose uptake when FTD patients were contrasted to FTD-MND patients. Our results suggest statistically comparable frontal and lateral temporal hypometabolism in both conditions but greater impairment of medial temporal lobe activity in FTD-MND. Our results and a review of the literature support the hypothesis that there is a functional continuum between classical motor neuron disease (cMND), FTD-MND, and FTD.