Experience seekers continuously pursue novel environmental stimuli, a tendency linked to genetic variation in mesolimbic dopamine transmission. However, the neuroanatomical basis accompanying these genetic and neurochemical associations is unknown. Animal and human experimental results suggest a central role for the hippocampus in processing novel stimuli. Here, we explored whether differences in human experience seeking are related to variations in hippocampal volume. High-resolution anatomic MR images were analyzed in 40 individuals who ranged from low through high on a validated experience seeking personality scale. Manual tracing analysis demonstrated positive correlation between right hippocampal volumes and scores on the experience seeking scale. A separate voxel-based morphometric analysis confirmed these results and localized the significant increase to the anterior portion of right hippocampal grey matter. We tested and were able to reject the possibility that results were mediated by a personality trait related to, but distinct from, experience seeking. The present data provide the first direct evidence for a relationship between human experience seeking and brain structure. In addition, these results provide new ecologically relevant evidence for a link between right anterior hippocampus and novelty processing.