To test the hypothesis that parathyroid hormone (PTH) regulates interleukin-6 (IL-6) expression locally in bone, the expression of IL-6 mRNA was examined by in situ hybridization after a subcutaneous injection of human PTH [1-84] (225 microg/kg) in 4-week old rats. Whereas IL-6 mRNA was not detected at the basal status, it was transiently detected in a subpopulation of stromal cells in the intertrabecular region of the metaphyses from 1/2 to 1 hr after PTH injection. Contrastingly, IL-6 transcripts were not detected in other cell populations at any time points examined. Since IL-6 is a known activator of osteoclasts, these results are consistent with the hypothesis that PTH stimulates the local IL-6 synthesis in stromal cells to indirectly activate osteoclasts.