AbstractCarriers of fragile X mental retardation 1 (FMR1) premutation alleles (55 to 200 CGG repeats) are generally spared the more serious neurodevelopmental problems associated with the full‐mutation carriers (>200 repeats) of fragile X syndrome. However, some adult male premutation carriers (55–200 repeats) develop a neurological syndrome involving intention tremor, ataxia, dementia, parkinsonism, and autonomic dysfunction. In excess of one‐third of male premutation carriers over 50 years of age develop the fragile X‐associated tremor/ataxia syndrome (FXTAS). FXTAS also represents a new form of inclusion disease, with eosinophilic intranuclear inclusions found throughout the brain in both neurons and astrocytes. Because FXTAS appears to be relatively specific to male premutation carriers, who are known to possess elevated levels of FMR1 mRNA, the neuropathology may arise as a consequence of a toxic gain‐of‐function of the mRNA itself, although this proposal requires additional direct testing. One of the critical needs at present is a better estimate for the prevalence of this disorder, because FXTAS is likely to be underdiagnosed in the adult movement disorders clinics. MRDD Research Reviews 2004;10:25–30. © 2004 Wiley‐Liss, Inc.