The role of the mediodorsal thalamic nucleus (MD) in spatial memory processes was assessed. Animals were preoperatively trained on an 8-arm maze placed in a visually deprived environment. Following 50 acquisition trials, one group received bilateral electrolytic lesion of the MD thalamus, whereas the other group received sham lesions. On postoperative tests of radial maze performance, MD lesioned animals made significantly more errors, made more errors sooner, and emitted fewer correct responses before making an error than did sham controls. The lesioned subjects also exhibited considerable perseveration immediately postoperation and developed response patterning on postlesion trials. Lesions of the mediodorsal thalamus may fundamentally compromise memory systems and alter ability to respond appropriately in a minimally cued environment.