The behavioral effects of radiofrequency lesions to the lateral internal medullary lamina region (IML) or the posterior region (Po: containing the parafascicular and posterior nuclei) of the thalamus were compared to sham operated controls. Subjects were pre-operatively trained and then tested for post-operative retention of a NMTP task. Whereas the Po-lesion group was impaired only on long delays (60, 90 s), the IML-lesion group was impaired on retention and re-acquisition and demonstrated lower performance at all delays (5-90 s) of the NMTP task. Post-operative training and testing was conducted on three additional tasks: Morris water maze, acoustic startle, and passive avoidance. The IML-lesion group was impaired in finding a hidden and visual platform in the Morris water maze, demonstrated a blunted response but normal habituation to an acoustic startle stimulus, and showed normal retention of a passive avoidance task. On those three tasks, the performance of the Po-lesion group was similar to controls. In the IML-lesion group, neuronal loss resulting from axotomy and/or transneuronal degeneration was observed within nuclei of the midline and anterior thalamus and the mammillary body. These results suggest that lesions to the IML region disrupt a range of cognitive functions and produce pathological destruction in distant brain regions; whereas damage to the posterior thalamus causes spatial delay-sensitive deficits.