Purified plasma membranes were prepared from normal rat livers. These membranes were unable to degrade parathyroid hormone (PTH), bovine PTH-(1-84) [bPTH-(1-84)], or bPTH-(1-34). The entire molecule bPTH-(1-84) caused a marked activation of adenylate cyclase (cAMP production increased over 5-fold), with half-maximal stimulation at 6.9 X 10(-8) M. The amino-terminal fragment bPTH-(1-34) was equipotent but gave a smaller maximal cAMP production. The human (h) amino acid sequence, hPTH-(1-34) was only weakly effective at a concentration of 10(-5) M. A similar species specificity was shown with crude rat renal cortical membranes. Of a variety of ligands, only glucagon and 10(-3) M F- were cyclase activators in these liver plasma membranes. Binding of [125I]iodo-bPTH by these membranes was fairly extensive but showed a saturation of binding only at high hormone concentrations (> 10(-6) M). Clearly, cleavage of the intact molecule PTH-(1-84) is not required for activation of the adenylate cyclase system of liver membranes. It appears that two rat tissues, liver and kidney, exhibit some species specificity in cyclase activation, i.e. the hPTH-(1-34) (Niall sequence) is inactive.