AbstractLesion studies on nonhuman primates utilizing recognition memory tests have shown that the orbitofrontal cortex is critical for the encoding of novel information, and anatomical studies have shown that the orbitofrontal cortex forms part of a mnemonic circuit that connects limbic medial temporal areas with higher‐order lateral frontal cortical regions. Furthermore, functional neuroimaging studies have demonstrated increased activity in the orbitofrontal cortex of the human brain during the encoding of novel visual and auditory information. The present positron emission tomography study examined brain activity related to the encoding of tactile information. Cerebral blood flow (CBF) in normal human subjects during the tactile exploration of novel stimuli from a related set of textures and patterns, as well as from a set of aversive tactile stimuli, was compared with CBF during a control condition involving familiar tactile stimuli. The results demonstrate that the right rostral orbitofrontal cortex is involved in the active encoding of novel tactile information, while a more caudal region of the orbitofrontal cortex, which is more closely connected with limbic and autonomic regions of the brain, was activated when subjects explored novel aversive tactile stimuli. These results suggest that the orbitofrontal cortex, through its connections with the limbic areas of the medial temporal lobe, influences the processing of incoming information and thus contributes to its encoding. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.