Exogenous toxins and chronic hypoxia have been implicated in the etiopathogenesis of a variety of neurological disorders, but it is not always possible to establish a cause-effect relationships. We describe a patient who presented with an unusual gait disorder and progressive motor neuron disease after residing for 2 years within Biosphere 2, a scientifically engineered dome, tightly sealed to allow miniscule exchange of air between its atmosphere and the earth's atmosphere. We postulate that this unusual syndrome resulted from chronic hypoxia possibly coupled with carbon monoxide and nitrous oxide exposure.