Background and purpose: Hypothalamic neuropeptides centrally modulate sexual arousal. However, the role of neuropeptides in peripheral arousal has been ignored. Vascular and non-vascular smooth muscle relaxation in the vagina is important for female sexual arousal. To date, in vitro studies have focused on vaginal strips with no studies on vaginal arteries. The aim of this study was to compare the effects of sexual hypothalamic neuropeptides on rabbit vaginal wall strips and arteries. Experimental approach: Tissue bath and wire myography techniques were used to measure isometric tension from strips and arteries, respectively. Key results: Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) relaxed both preparations, effects that were only antagonized by the VIP/PACAP antagonist VIP6-28 (10 nM) and the PAC 1 antagonist PACAP 6-38 (1 mM). The melanocortin agonist a-melanocortin-stimulating hormone (1 mM), but not bremelanotide (1 mM), also relaxed both preparations.