SAMP6 mice are a murine model for senile osteoporosis, characterized by low peak bone mass seen at 4 or 5 months of age. Parathyroid hormone (PTH)-induced c-fos expression was examined in the bones, bone-marrow cells and kidney tissues of 2-month-old male SAMP6 mice. SAMP2 mice, which have a higher peak bone mass, were used as controls. The expression of c-fos in the bone peaked at 30 min after 60 microg/kg of human PTH(1-34) administration. After peaking, the expression fell quickly in SAMP2 mice. This decrease in expression was delayed in SAMP6 mice and the expression was higher at 1 h than in SAMP2 mice. The phenomenon observed in the bone appears to be tissue specific as it was not seen in the bone-marrow cells or kidney tissue. Immunohistochemical studies showed that c-Fos protein was localized to the nuclei of some of the osteocytes and a few of the osteoblasts in the cortical bone, and that osteocytes expressing c-Fos protein increased after PTH treatment. These results suggest that osteocytes might contribute to the maintenance of higher levels of c-fos expression in the bones of SAMP6 mice and may be related to cortical osteopenia in these mice by modulating bone remodeling and/or modeling.