The identification of specific, diagnostically useful predictors of protein dysfunction in the frontotemporal lobar degenerations (FTLD) is a problem of great clinical and biological interest. Correlations between regional patterns of tissue loss and specific proteinopathies have not been established. Specific brain imaging correlates of protein tau dysfunction were sought using voxel-based morphometry in FTLD subgroups with and without tau pathology. Seventeen patients with pathologically or genetically confirmed diagnoses of FTLD who had undergone volumetric brain magnetic resonance imaging (MRI) were identified retrospectively and tau-positive (n = 9) and tau-negative (n = 8) subgroups were defined. MRI data were compared with healthy age- and sex-matched controls using voxel-based morphometry implemented in a statistical parametric mapping software package. Compared with controls, tau-positive and tau-negative subgroups had extensive common areas of regional brain atrophy predominantly affecting the frontal and anterior temporal lobes. No specific brain imaging features were identified for either subgroup. Patterns of frontotemporal atrophy do not predict the presence or absence of tau pathology; conversely, different immunohistochemical profiles are associated with similar patterns of regional vulnerability to neuronal loss in FTLD. Copyright 2004 S. Karger AG, Basel.