The metabolism of added N-terminal and C-terminal synthetic human PTH (synhPTH) fragments was studied in isolated perfused rat livers and in filtering and nonfiltering kidneys. Initial concentrations: synhPTH-(1-34), 14 pmol/liter, synhPTH-(39-84) 85 pmol/liter, synhPTH-(1-84) 3 pmol/liter, or 1000 pmol/liter of each fragment and intact PTH. Clearances were measured by assays specific for intact PTH, N-terminal, midmolecule, and C-terminal immunoreactive PTH. Metabolism of the added PTH into smaller circulating fragments was analyzed by HPLC. The clearance of synhPTH-(1-34) in the filtering kidneys was not significantly different from the clearance of synhPTH-(39-84) and inulin, and HPLC demonstrated no metabolism of synhPTH-(1-34) or synhPTH-(39-84) in the kidneys. The livers did not clear synhPTH-(39-84), while the clearance of synhPTH-(1-34) was significant (P < 0.005). HPLC demonstrated no metabolism of synhPTH-(39-84) by the livers, but extensive metabolism of synhPTH-(1-34). The livers cleared synhPTH-(1-34) significantly (P < 0.05) faster than synhPTH-(1-84). In conclusion, the kidneys cleared N-terminal PTH fragments at the same rate as C-terminal fragments mainly by filtration. The livers cleared N-terminal fragments faster than intact PTH, but did not clear C-terminal fragments. This differential hepatic clearance may play a major role in maintaining the differences between the circulating levels of N-terminal and C-terminal immunoreactive PTH.