In the present study treatment of IBMX, a phosphodiesterase (PDE) inhibitor, alone induced osteoclast formation in co-cultures of mouse bone marrow cells and calvarial osteoblasts. However, treatment of IBMX in combination with prostaglandin $E_2;(PGE_2)$ inhibited osteoclast formation in a dose-dependent manner. Among various isozyme-specific PDE inhibitors, a PDE4 specific inhibitor, rolipram, showed similar effects as IBMX on osteoclast formation. To address the involvement of cyclic adenosine monophosphate (cAMP) in osteoclast formation, cAMP concentration in calvarial osteoblasts was investigated. When calvarial osteoblasts were co-cultured with IBMX alone or in combination with $PGE_2$, the patterns of cAMP concentration in calvarial osteoblasts were differ each other suggesting that cAMP in calvarial osteoblasts subtly regulates osteoclast formation.