In the 1950s, Mertz and Schwarz published a series of experiments providing evidence that chromium (Cr) is an essential nutrient forming the active component of the "glucose tolerance factor." This factor enhances the binding of insulin to its receptors, potentiating the action of insulin on carbohydrate metabolism. Cr deficiency in patients on total parenteral nutrition (TPN) is associated with the development of glucose intolerance, glycosuria, weight loss, peripheral neuropathy, ataxia, and encephalopathy. In these patients, the infusion of trivalent Cr has resulted in a resolution of neurological changes and re-establishment of glucose tolerance. Recently, others have cautioned against the administration of Cr in parenteral nutrition, because it is a contaminant of parenteral nutrition solutions and also because circulating Cr levels have been found to be elevated in patients on parenteral nutrition. However, no relationship was noted between the response to Cr in these patients and their plasma levels. This observation was recently confirmed in another patient with severe neuropathy and glucose intolerance who responded to Cr infusion despite high plasma levels of Cr. Plasma levels may not be appropriate for the assessment of Cr status in patients receiving TPN. The development of unexpected glucose intolerance and/or neuropathy would suggest the presence of Cr deficiency. In such patients, the diagnosis of deficiency by infusing Cr daily for 2 weeks to correct an abnormal glucose tolerance will confirm the diagnosis of Cr deficiency. The subsequent improvement in neuropathy, when present, following the administration of Cr would support this diagnosis.