It is generally considered that osteoblastic cells are essential for osteoclast formation. We tested the ability of hemopoietic tissue to differentiate osteoclastic characteristics in the absence of osteoblastic cells. We found that large numbers of calcitonin-receptor positive (CTRP) cells can be induced by prostaglandin E2 and 1,25(OH)2 vitamin D3, in cultures of hemopoietic mouse spleen. Moreover, spleen stromal cells were equivalent to bone marrow stromal cells in CTRP-cell induction. The spleen CTRP cells did not resorb bone, but were rapidly induced to full resorptive activity upon osteoblast addition. Thus, bone cells may not be essential for osteoclast formation, but rather are required to activate and regulate the resorptive function of mature osteoclasts.