Previous studies have shown that parathyroid hormone (PTH) stimulates bone formation and completely restores lost cancellous bone at skeletal sites with moderate osteopenia in relatively young ovariectomized (OVX) rats. The current study was designed to determine whether PTH has similar bone anabolic effects in aged OVX rats and to compare the bone restorative response to PTH at skeletal sites with moderate and severe osteopenia. Female Sprague-Dawley rats were subjected to sham surgery or bilateral ovariectomy at 3 months of age and maintained untreated for the first year after surgery to allow for the development of moderate vertebral osteopenia and severe tibial osteopenia in OVX rats. Groups of baseline control and OVX rats were sacrificed at the end of this pretreatment period. The remaining OVX rats were then treated for 10 weeks with vehicle, antiresorptive agents alone (estrogen, the bisphosphonate risedronate, or calcitonin) or PTH alone. Other groups of OVX rats were treated concurrently with PTH and each of the antiresorptive agents. As expected, the proximal tibia of baseline OVX rats exhibited severe cancellous osteopenia, whereas the first lumbar vertebral body was moderately osteopenic. Treatment of OVX rats with antiresorptive agents alone failed to restore cancellous bone at both skeletal sites, whereas treatment with PTH alone markedly stimulated bone formation and completely restored lost cancellous bone in the lumbar vertebra. PTH also stimulated bone formation in the severely osteopenic proximal tibia of OVX rats but only marginally restored lost cancellous bone, possibly due to an inadequate number of bone spicules to serve as a foundation for new bone formation. Concurrent treatments with PTH and antiresorptive agents did not augment cancellous bone to a greater, or lesser, extent than treatment with PTH alone. The positive results from the moderately osteopenic lumbar vertebra indicate that cancellous bone of aged OVX rats retains its ability to respond anabolically to PTH. However, the negative results from the severely osteopenic proximal tibia of aged OVX rats may provide insight into the failure of the skeletons of some osteoporotic patients to respond adequately to anabolic agents such as fluoride or PTH.