Dura-Guard Dural Repair Patch, PRECLUDE Dura Substitute, and Codman ETHISORB Dura Patch were evaluated in a six-month dural tissue reaction study in rabbits. Bilateral craniotomy was followed by subdural implantation for each dura mater substitute. The surgical procedure for the sham control group was the same except that no material was implanted. Implantation of all of these dura mater substitutes for 28, 91, or 182 days post-implantation did not result in any deaths or clinical neurobehavioral abnormalities, changes in cerebrospinal fluid, or significant macroscopic changes at necropsy. However, histomorphologic evaluation of the implantation sites revealed some differences in the tissue response to these materials. For Dura-Guard Dural Repair Patch, a nonabsorbable material derived from bovine pericardium, the implantation site was characterized by fibrosis of the overlying area with islands of osseous metaplasia and adhesions to the brain surface. Over time, infiltrative fibrosis of the implant resulted in separation of the collagenous layers of the implant and compression of the underlying brain. Fibrosis of the overlying area that incorporated this material formed a 'replacement' dura mater. Adhesions to the brain surface observed initially were still present at six months post-implantation. Implantation of PRECLUDE Dura Substitute, a nonabsorbable material comprised of expanded polytetrafluoroethylene, resulted in virtually no early reaction, and few adhesions to the brain surface at any time period. Although this material was eventually incorporated by fibrosis, islands of osseous metaplasia were also observed in this 'replacement' dura mater. The tissue reaction to Codman ETHISORB Dura Patch, an absorbable material comprised of polyglactin 910 and polydioxanone, was generally characterized by low-grade granulomatous inflammation and initial adhesions to the brain surface. The three-dimensional structure of this implant acted as a scaffold to guide the development and integration of a 'replacement' dura mater. The absorption of the material was associated with complete resolution of the inflammatory reaction, a lack of cerebral adhesions, and restoration of the normal architecture of this region. In conclusion, subdural implantation of Dura-Guard Dural Repair Patch, PRECLUDE Dura Substitute, or Codman ETHISORB Dura Patch in rabbits for up to six months resulted in the eventual restoration of the dura mater without significant adverse effects. However, osseous metaplasia associated with nonabsorbable Dura-Guard Dural Repair Patch and PRECLUDE Dura Substitute, and the infiltration of Dura-Guard Dural Repair Patch by fibrosis suggests that long-term follow-up may be needed after the use of these materials in patients. An advantage of Codman ETHISORB Dura Patch was that it was completely absorbed after guiding the restoration of the dura mater without any morphological sequelae.