The effect of five peptides derived from the C-terminal portion of rat pro-VGF (VGF(577-617), VGF(588-617), VGF(599-617), VGF(556-576) and VGF(588-597)) on penile erection was studied after injection into the hypothalamic paraventricular nucleus of male rats. VGF(577-617), VGF(588-617), VGF(599-617) and, to a lower extent, VGF(588-597) (0.1-2 microg) induced penile erection episodes in a dose-dependent manner when injected into the paraventricular nucleus, while VGF(556-576) was ineffective. VGF(588-617)-induced penile erection was reduced by nitro(omega)-L-arginine methylester (L-NAME; 20 microg), by morphine (5 microg) and by muscimol (1 microg), but not by dizocilpine [(+)MK-801; 1 microg], nor by cis-flupenthixol (10 microg) given into the paraventricular nucleus 10 min before the VGF peptide. d(CH2)5Tyr(Me)-Orn8-vasotocin (1 microg) effectively reduced VGF(588-617)-induced penile erection when given into the lateral ventricles but not when injected into the paraventricular nucleus. Immunocytochemistry with antibodies specific for the C-terminal nonapeptide sequence of pro-VGF (VGF(609-617)) revealed numerous neuronal fibres and terminals within the paraventricular nucleus, including its parvocellular components. Here, many immunostained neuronal terminals impinged on parvocellular oxytocinergic neurons. The present results show for the first time that certain pro-VGF C-terminus-derived peptides promote penile erection when injected into the paraventricular nucleus and suggest that, within this nucleus, these or closely related pro-VGF-derived peptides may be released to influence sexual function by activating paraventricular oxytocinergic neurons mediating penile erection.