The role of cAMP and calcium in the induction of ornithine decarboxylase (ODC, E.C.18.104.22.168) activity in the osteogenic sarcoma cell line, UMR 106‐01, was studied, with particular interest for parathyroid hormone (PTH). PTH and forskolin dose‐dependently induced the ODC activity and the cAMP production. Protein synthesis is involved in the effect of PTH and forskolin on ODC activity but not on cAMP production. Using quin2 we showed that 20 nM PTH and 10 μM forskolin increased the intracellular ionized calcium concentration ([Ca2+]i), thereby offering the possibility for calcium to play a role as cellular mediator in the action of PTH and forskolin in bone. Data obtained with A23187 showed that solely an increase of the [Ca2+]i is not sufficient to stimulate basal or potentiate PTH‐ and forskolin‐induced ODC activity. However, the effects of calcium channel blockers and EGTA on basal and PTH‐ and forskolin‐induced ODC activity point to a specific role for calcium. Moreover, the effects of calcium channel blockers and EGTA on basal and PTH‐ and forskolin‐induced cAMP production indicate that the involvement of calcium in the induction of ODC activity is primarily located at another site than the adenylate cyclase. These data indicate that calcium is involved in the control of basal ODC activity. Furthermore, these data suggest that both cAMP and calcium are involved in the induction of ODC activity by PTH and forskolin. More precisely, ODC activity in UMR 106‐01 cells can be induced by PTH and forskolin via a calcium‐dependent cAMP messenger system.