The hypothalamic, peptide hormone, oxytocin (OXT), is a powerful modulator of social-, stress- and anxiety-related behaviors, as is the brainstem, neuropeptide relaxin-3 (RLN3). Recent studies indicate the involvement of KCNQ potassium channels in neuronal OXT and RLN3 signaling, with these neuropeptides displaying opposing excitatory and inhibitory actions, respectively. OXT receptors (OXTR) and RLN3 receptors (RXFP3) are expressed by neurons in the rat ventral hippocampal CA3 area (vCA3), which is involved in social behavior and anxiety control; but the possible interaction between OXT and RLN3 signaling in modulating vCA3 activity has not been investigated. Therefore, we verified the neurochemical nature of OXTR and RXFP3 mRNA-expressing vCA3 neurons, using fluorescence in situ hybridization (ISH), and examined the effects of OXTR and RXFP3 activation on vCA3 activity, using ex vivo multielectrode array (MEA) and patch-clamp recordings. ISH revealed that the majority of OXTR mRNA-positive neurons co-expressed vGAT1 mRNA (vGAT1+) and 20% of vGAT1+ neurons co-expressed RXFP3 and OXTR mRNA. Notably, both vGAT1+ and vGLUT2+ vCA3 neurons expressed RXFP3 mRNA. MEA and patch-clamp recordings revealed an excitatory effect of OXTR activation and an inhibitory effect of RXFP3 activation on vCA3 neurons, which were both significantly reduced by the selective, KCNQ blocker, XE-911.​These data reveal that OXT/OXTR and RLN3/RXFP3 signaling have opposite effects on specific populations of vCA3 neurons by differentially modulating KCNQ channels, and studies are now required to determine the precise molecular mechanisms involved and how these interactions affect behavior. Funding: National Science Centre, Poland (UMO-2018/30/E/NZ4/00687; UMO-2023/49/B/NZ4/01885)