A 36-year-old man with ankylosing spondylitis, amyloidosis and chronic renal failure on maintenance hemodialysis developed severe hypoglycemia while being treated with propoxyphene. Upon discontinuation of the drug blood glucose levels returned to normal and hypoglycemia did not recur. Simultaneously with hypoglycemia, plasma glucagon and growth hormone levels were appropriately raised and serum insulin levels were adequately suppressed, thus ruling out hyperinsulinemia as the cause of hypoglycemia. A review of the literature disclosed four similar cases of propoxyphene-induced hypoglycemia, two of them with renal dysfunction. Propoxyphene should be remembered as a potential cause of hypoglycemia, particularly in patients with renal failure.