Intravenous injection of chicks with bovine parathyroid hormone (1-34) (3.3 micrograms/100 g body wt.) or 16,16-dimethyl PGE2 (5 micrograms/100 g body wt.) caused rapid (3 minute) net inhibition of 45Ca uptake into femur and calvarium. These agents also elevated bone adenosine 3',5'-cyclic monophosphate (cAMP) but not guanosine 3',5'-cyclic monophosphate (cGMP) levels at this time. Methylxanthine phosphodiesterase inhibitors (MXPI), caffeine, theophylline, and 3-isobutyl-1-methylxanthine (IBMX) (0.3-5 mg/100 g body wt.) similarly inhibited net 45Ca uptake into femur and to a lesser extent calvarium. Plasma 45Ca and total Ca levels were unaltered or showed a slight tendency to be increased over control values 3 minutes after injection. However, the effects of the non-MXPI, dibutyryl-cAMP (0.5-5 mg/100 g body wt.) on bone 45Ca uptake were negligible. Of the MXPI, only IBMX elevated total cAMP levels in chick bone at 3 minutes. These data implicate but do not confirm a mediatory role for cAMP in the rapid inhibitory actions of PTH and PGEs on bone net 45Ca uptake in chicks.