The in vivo responsiveness of small arterioles to the topical administration of two parathyroid hormone fragments was investigated using television microscopy. Male Sprague-Dawley rats were anesthetized with sodium pentobarbital (50 mg/kg) and second- and third-order arterioles in the cremaster muscle were exposed to increasing concentrations (2 X 10(-5) to 6 X 10(-4) mg/ml) of either hPTH (1-34) or bPTH-(3-34). Second- and third-order arterioles within the cremaster dilated (183% and 281% of control, respectively) following exposure to PTH-(1-34) in bath concentration of 10(-4) mg/ml and above. The dilation associated with PTH administration was abolished in second-order and greatly attenuated for third-order arterioles when the first two amino acid residues of the PTH molecule were removed (PTH (3-34) fragment). Inhibition of endogenous prostaglandins synthesis with mefenamic acid did not attenuate the vasodilator response to PTH. However, exposure to the muscarinic blocking agent atropine (10(-7) g/ml) totally inhibited the dilator response to PTH-(1-34). These data suggest that PTH induces arteriolar dilation by stimulation of muscarinic receptors in the vasculature possibly by causing the release of endogenous acetylcholine.