The microtubule-associated protein Tau (MAPT) gene codes for the protein Tau that is involved in the pathogenesis of neurodegenerative diseases. Recent studies have detected an over-representation of the H1 haplotype of the MAPT gene in neurodegenerative disorders such as progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), frontotemporal dementia (FTD) and Parkinson's disease (PD), whereas the H2 haplotype has been found to be related to familial FTD. We aimed to investigate the association between MAPT haplotype status and brain morphology in healthy adults. A total of 150 healthy subjects underwent 3D high-resolution magnetic resonance (MR). MR images were processed following an optimized protocol to perform the Voxel-based morphometry (VBM) comparisons of the gray matter (GM) in H1 carriers (n=141) in contrast to H2H2 homozygous (n=9), and H1H1 homozygous (n=85) in contrast to H2 carriers (n=65). The threshold for statistical significance was 0.005 uncorrected. Opposite comparisons were also carried out. The groups had similar demographic and cognitive features. Compared with H2H2, the H1 carriers showed up to 19% smaller GM volume in the head of the right caudate nucleus, in the right middle frontal gyrus, in the left insula and orbito-frontal cortex, and in the inferior temporal and inferior cerebellar lobes, bilaterally. Compared with all H2 carriers, H1H1 displayed lower GM in the same regions, but the effect was smaller (5%), possibly due to a dilution effect by H1 in the H2 carriers group. The data suggest that H1 haplotype is associated with a particular cerebral morphology that may increase the susceptibility of the healthy carriers to develop neurodegenerative diseases such as sporadic tauopathies.