Persistent hypoglycemia occasionally is associated with tumors of many types. Usually these tumors are of large size and often are of mesenchymal origin. There is evidence of increased glucose uptake from the blood, some of which may occur in the tumor itself. In addition, hepatic glucose production may also be impaired. While increased levels of insulin have never been unequivocally established in the plasma of these patients, a number of insulin-like peptides have been reported. One such peptide may be related to insulin-like growth factor II, but reports from different laboratories are conflicting. Recently, the possible role of oncogenes in stimulating tumor glucose metabolism and tissue necrosis factor and other cytokines in stimulating general glucose uptake have received attention. Treatment of the condition includes surgery, radiation, or chemotherapy directed at the primary tumor and supportive measures with increased glucose administration and corticosteroids.