The individual and combined effects of intact PTH, amino-terminal, and a series of truncated carboxyl-terminal PTH fragments on alkaline phosphatase activity were examined in dexamethasone-treated rat osteoblastic osteosarcoma cells ROS 17/2.8. Dexamethasone-induced alkaline phosphatase activity was inhibited not only by hPTH(1–84) and amino-terminal PTH fragment hPTH(1–34), but also by carboxyl-terminal PTH fragment hPTH(69–84) in a dose-related fashion. At 10−7 mol/1, hPTH(1–84) completely abolished dexamethasone-induced alkaline phosphatase activity, while hPTH(1–34) and hPTH(69–84) reduced alkaline phosphatase activity to 0.16±0.02 and 0.80±0.03 fold, respectively, of the control value obtained in the absence of PTH peptides. The combination of hPTH(1–34) and hPTH(69—84) resulted in reduction of alkaline phosphatase activity to the level obtained by hPTH(1-84). The shorter carboxyl-terminal PTH fragment hPTH(71–84) did not affect alkaline phosphatase activity or modulate the action of hPTH(1–34). The longer carboxyl-terminal PTH fragment hPTH(53-84) stimulated alkaline phosphatase activity up to 1.23±0.03 fold and partially blunted the inhibitory effect of hPTH(1–34) on alkaline phosphatase activity. These findings suggest that carboxyl-terminal PTH fragments could exert diverse effects on the target cells, depending on the length of deletion of amino-terminal amino acids of PTH molecule, and interact with amino-terminal PTH fragment. The two amino-terminal amino acids of hPTH(69–84) and the 53–68 portion of hPTH(53–84) might be responsible for the respective inhibitory and stimulatory effects of the peptides on alkaline phosphatase activity.