We have studied the effect of parathyroid hormone (PTH) on adenylate cyclase of microvessels isolated from rat cerebral cortex. Native bovine (b) PTH-(1-84), the synthetic amino-terminal fragment bPTH-(1-34) and the synthetic analog [Nle8,Nle18,Tyr34]-bPTH- (1-34) amide stimulated adenylate cyclase in a dose-dependent manner with apparent ED50 values of 16 nM, 6.3 nM and 15 nM respectively. The stimulation by bPTH was greatly enhanced by guanosine triphosphate. The PTH antagonist, [Nle8,Nle18,Tyr34]-bPTH-(3-34) amide inhibited the action of bPTH-(1-84) and bPTH-(1-34). In summary, PTH stimulated adenylate cyclase in rat cerebral microvessels in a very similar manner to its stimulation in the renal cortex.