An outbreak of chronic fatigue syndrome linked with sick building syndrome was recently described as a new association. Whether chronic fatigue syndrome acquired in this setting tends to remit or, as sporadic cases often do, persist, is unknown. To clarify the natural history of chronic fatigue syndrome in association with sick building syndrome the 23 individuals involved in the outbreak were interviewed four years after the onset. In the previous interview one year after the onset of symptoms, 15 (including 5 with chronic fatigue syndrome and 10 with idiopathic chronic fatigue) of the 23 noted fatigue. Three years later 10 of the 15 were "fatigue free" or "much improved". Five were only "some better", "the same", or "worse". Three of the five people previously diagnosed with chronic fatigue syndrome were "much improved" (two) or "fatigue free" (one). The remaining two were seriously impaired, homebound and unable to work. The 10 individuals with substantially improved fatigue (three of the five with chronic fatigue syndrome and seven of the 10 with idiopathic chronic fatigue) were more likely to have noted improvement in nasal and sinus symptoms, sore throats, headaches, and tender cervical lymph nodes when compared to those with a lingering significant fatigue (p < 0.001). Upper respiratory symptoms and headaches improved in those with reduced fatigue but remained problematic in those with persisting significant fatigue. We conclude that the fatigue related to sick building syndrome, including chronic fatigue syndrome, is significantly more likely to improve than fatigue identified in sporadic cases of chronic fatigue syndrome.