Corticotropin-releasing hormone (CRH)-containing neurons in the paraventricular nucleus (PVN) in the hypothalamus of multiple sclerosis (MS) patients are hyperactivated. Since interleukin-1 (IL-1)β is a powerful activator of CRH neurons, its immunohistochemical expression was studied in the postmortem hypothalamus of MS patients (n=11) and matched controls (n=11). Hypothalamic tissue of 10/11 MS patients showed demyelinating lesions that in many cases contained IL-1β-immunoreactive (ir) macrophages and glial cells. In control subjects IL-1β-ir was only sporadically found in glial cells. Interestingly, abundant IL-1β-ir was also present in hypothalamic neurons. Neuronal IL-1β co-localised with oxytocin and not with vasopressin or CRH. IL-1β clearly yielded a less intense staining in neurons and numbers of IL-1-ir neurons in the PVN were 4.5-fold reduced in MS. We suggest that IL-1β produced by activated glial cells in the hypothalamus of MS patients may contribute to the activation of the hypothalamic CRH neurons, while reduced expression of neuronal IL-1β in MS patients may have consequences for neuroendocrine, behavioural or autonomic functioning. Copyright (C) 2000 Elsevier Science B.V.