Background: Adenosine triphosphate (ATP)-sensitive potassium channels (KATP) are important modulators of vascular tone. Preliminary data from our laboratory suggests that KATP channels are expressed in the fetoplacental vasculature where addition of pinacidil, a specific K ATP opener, promotes relaxation. We aimed to assess the effects of KRN2391 and KRN4884 on the fetoplacental vasculature, which are putative K ATP channel openers. Materials and methods: Functional activity of KATP channels was assessed in chorionic plate arteries and veins using wire myography. Cromakalim-, KRN2391- and KRN4884-induced relaxations were assessed in the presence and absence of agonist-induced pretone. Cromakalim, an established KATP channel opener, acted as control. Results: KRN2391 evoked significantly greater relaxation of chorionic plate arteries and veins than either KRN4884 or cromakalim. KRN2391-induced relaxation of precontracted arteries and veins was reduced in the presence of inhibitiors of the nitric oxide pathway (L-NNA or LY83583). With KRN4884, there was no contribution of nitric oxide to the induced relaxation. Conclusions: We conclude that K ATP channels play an important role in controlling placental vascular tone. KRN2391 induces relaxation of human placental blood vessels by activation of KATP channels and via activation of nitric oxide-dependent pathways. © 2007 The Authors.