Nesfatin-1 is a newly-discovered satiety peptide found in several nuclei of the hypothalamus, including the paraventricular nucleus. To begin to understand the physiological mechanisms underlying these satiety-inducing actions, we examined the effects of nesfatin-1 on the excitability of neurones in the paraventricular nucleus. Whole-cell current-clamp recordings from rat paraventricular nucleus neurones showed nesfatin-1 to have either hyperpolarising or depolarising effects on the majority of neurones tested. Both types of response were observed in neurones irrespective of classification based on electrophysiological fingerprint (magnocellular, neuroendocrine or pre-autonomic) or molecular phenotype (vasopressin, oxytocin, corticotrophin-releasing hormone, thyrotrophin-releasing hormone or vesicular glutamate transporter), determined using single cell reverse transcription-poylmerase chain reaction. Consequently, we provide the first evidence that this peptide, which is produced in the paraventricular nucleus, has effects on the membrane potential of a large proportion of different subpopulations of neurones located in this nucleus, and therefore identify nesfatin-1 as a potentially important regulator of paraventricular nucleus output.