The nucleus incertus (NI) is a discrete brainstem structure located adjacent to the 4th ventricle in the ventromedial central grey of mammalian brain. NI neurons in rat brain are primarily GABAergic, but synthesize neuropeptides including relaxin-3 [1] and widely innervate many brain areas, including the septohippocampal network and associated hypothalamic and limbic circuits [2]. Initial functional studies suggest a role for NI/relaxin-3 neurons in the control of stress responses, arousal/sleep, feeding/metabolism and spatial/emotional memory (see [3]). However, the nature of the interactions between NI/relaxin-3 neurons and other neural circuits/signalling systems controlling these functions are unknown. Data from our recent in vitro experiments demonstrate direct responses of NI neurons to several peptide transmitters (hormones), reflecting neural and neurohumoral inputs, including strong depolarisation by the stress peptide, CRF, and by the multi-functional peptides, orexin, dynorphin and ghrelin. Furthermore, the strong effect on feeding/(body weight) of acute/(chronic) central administration of relaxin-3 or selective RXFP3 agonist peptides, is hypothesized to be mediated through inhibition of hypothalamic oxytocin (and vasopressin) neurons (see [4,5]). Notably, in separate in vitro patch clamp experiments, we observed that the RXFP3 agonist, RXFP3-A2, inhibited paraventricular nucleus neurons, including those containing oxytocin. Our data provide evidence in support of the hypothesis that relaxin-3/RXFP3 signalling is associated with acute and/or chronic stress and feeding/metabolic-related abnormalities, including obesity and binge eating disorders.