SUMMARYWe have previously demonstrated that intravenous injection of synthetic bovine parathyroid hormone (bPTH(1-34)), but not necessarily bPTH(l-84), into chicks rapidly (3 min) inhibits skeletal uptake of an acute 45Ca label. In the present study hydrogen peroxide oxidation of bPTH(I-34) abolished this response and reduced its ability to activate adenylate cyclase in bone and kidney. Oxidised bPTH(I-34) did, however, exhibit the full hypercalcaemic activity of untreated hormone. In contrast, the analogue [Nle8, Nle'8, Tyr34]-bPTH(l-34)amide reduced chick bone 45Ca uptake but failed to raise plasma Ca levels. Cyclic AMP formation in response to this analogue was also slight. Another analogue, [Nle8, Nle'8, Tyr34]-bPTH(3-34)amide, failed to inhibit 45Ca uptake or stimulate cyclic AMP formation in chick bone. It was also without hypercalcaemic activity. These data suggest that the hypercalcaemic response to bPTH(1-34) in chicks is not merely a reflection of its inhibitory effect on bone 45Ca uptake. They also question the relevance of cyclic AMP in the former action. A model is proposed by which PTH could rapidly inhibit bone net 45Ca uptake by stimulating release and turnover of intracellular calcium stores in bone lining cells, thereby creating a gradient for Ca out of bone.