I've been wondering this for a while so thought I'd put it out for consideration to the group. I'd be particularly interested to hear from @Jonathan Edwards and any other residents doctors / retired doctors we have in our midst. I spent a lot of (pointless) time the past year looking for a diagnosis that fit my symptoms - I'm sure a lot of us have. One I kept coming back to was the various vasculidities but I ultimately concluded that given their rarity and a with (in my case) a normal ESR, CRP, WCC and no hematuria that it was highly improbable. Nevertheless, of all the strange diseases I've been looking at, vasculitis seemed (to my un-medical brain) to fit the CFS/ME bill the best. (There's one other blog post on the net that wonders this also). This does nothing, of course, for treatment (unless we can managed to get diagnosed) but I wanted to see if anyone else thought the hypothesis was credible. Reasoning for: CFS/ME is characterized by three key dysfunctions: neurological, circulatory/cardiovascular and immunological. Vasculitis can easily explain the first two through recurrent ischemic damage to the brain stem (or other parts of the brain) and the heart; as an autoimmune disease, I presume that dysfunctional immunity would be expected. The pathogenesis of the vasculidities seems something of a mystery, but viral infections seem to be implicated in the majority of cases (this is true, of course, of many other autoimmune diseases). Although unlikely, vasculitis occasionally can have normal inflammatory markers (example case report), but most doctors will follow the rule that 99% of the time a normal ESR strongly argues against the diagnosis and mark it off the differential. In such a situation, it would seem highly unlikely that any doctor would risk performing a blood vessel biopsy. The success of the rituximab trials would be consistent with CFS/ME being a vasculitis. Many of us report symptoms such as chronic sinusitis, prostatitis, etc, which would be consistent with vasculitis. Reasoning against: Our generally normal inflammatory markers. Generally, we lack major renal or liver disease (however not all vasculidities attack these organs) and chest x-rays are also normal. Supposed rarity of vasculidities (although perhaps, given the 'protean nature' of their presentations, perhaps they are underdiagnosed?). We also lack major vasculitic skin findings. Although some of the things many of us report (such as bier spots) could seem consistent with a vasculitic process. I know that most of the twenty or so vasculidities have specific findings (e.g. mouth ulcers in Behcet's; absent pulses in Takayasu's). The idea I'm putting out isn't so much that a subset of CFS/ME is an undiagnosed form of an established vasculitis so much as that perhaps it is one which hasn't been recognized as such yet. Maybe this might only apply to a subset of patients, but perhaps CFS/ME being a subclinical (or undiagnosed) systemic vasculitis could be an explanation for some.