Idiopathic environmental intolerance (IEI), also known as multiple chemical sensitivity, is a clinical description for a cluster of symptoms of unknown etiology that have been attributed by patients to multiple environmental exposures when other medical explanations have been excluded. Because allergy has not been clearly demonstrated and current toxicological paradigms for exposure-symptom relationships do not readily accommodate IEI, psychogenic theories have been the focus of a number of investigations. A significantly higher lifetime prevalence of major depression, mood disorders, anxiety disorders, and somatization disorder has been reported among patients with environmental illness compared with that in controls. Symptoms often include anxiety, lightheadedness, impaired mentation, poor coordination, breathlessness (without wheezing), tremor, and abdominal discomfort. Responses to intravenous sodium lactate challenge or single-breath inhalation of 35% carbon dioxide versus a similar breath inhalation of clean air have shown a greater frequency of panic responses in subjects with IEI than in control subjects, although such responses did not occur in all subjects. Preliminary genetic findings suggest an increased frequency of a common genotype with panic disorder patients. The panic responses in a significant proportion of IEI patients opens a therapeutic window of opportunity. Patients in whom panic responses may at least be a contributing factor to their symptoms might be responsive to intervention with psychotherapy to enable their desensitization or deconditioning of responses to odors and other triggers, and/or may be helped by anxiolytic medications, relaxation training, and counseling for stress management.