This Notice of Funding Opportunity (NOFO) invites applications for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Collaborative Research Centers (CRC). The overarching goal of this initiative is to support a network of Centers that will work collaboratively to define the cause(s) of and discover improved treatments for ME/CFS. A more immediate goal for each Center is to rapidly advance synergistic, interdisciplinary research programs while serving as local resources and national leaders in ME/CFS research. Successful CRC research programs will facilitate research in ME/CFS through conducting of 1) collaborative basic and/or clinical research on ME/CFS; 2) longitudinal studies of individuals with ME/CFS within each ME/CFS CRC and across CRCs within the network; 3) access to information related to ME/CFS for basic and clinical researchers, academic and practicing physicians, healthcare professionals, patients, and the lay public. Data sharing will be required through the separate data management and coordinating center (DMCC) and biospecimens will be required to be deposited, stored and shared through NIH-supported biorepositories. Funding decisions will focus on those applications most likely to make highly impactful contributions to ME/CFS research, as well as on those with the greatest potential to collaborate effectively across the ME/CFS CRC program.