: Ghrelin, an orexigenic peptide, exerts immunomodulatory and other effects in the CNS and has neuroprotective properties. Ghrelin is predominantly produced by X/A-like cells in the gastric mucosa. Hence, ghrelin's main source of production lies outside the CNS while important functions of ghrelin are operated by specific receptors in the CNS. We analyzed 82 samples of our repository (45 samples form patients with multiple sclerosis and 37 control samples) for cerebrospinal fluid (CSF) and corresponding serum concentrations of ghrelin. Desacyl ghrelin concentrations were measured with a commercially available enzyme immunometric assay. We validated the assay for CSF samples. The test-retest reproducibility for ghrelin in CSF samples was excellent. Ghrelin CSF concentrations were higher in patients with multiple sclerosis (p<0.02) compared with controls. CSF concentrations correlated with serum concentrations in patients with multiple sclerosis (p<0.01). No such correlation was found in controls. Our findings endorse existing hypotheses that ghrelin affects the central inflammatory process in MS. The correlation between serum and CSF concentrations in MS, but not in controls, suggests a differential regulation of blood-to-brain transport mechanisms for ghrelin in MS and indicates that central effects of ghrelin in MS might be amenable to pharmacological manipulation of the systemic ghrelin secretion.