A woman with diabetes mellitus, compensated chronic renal insufficiency and multiple episodes of fasting hypoglycemia was studied. On fasting, despite appropriate insulin, glucagon and normal lactate levels, this patient developed early, profound hypoalaninemia followed by hypoglycemia. Glucose and alanine turnover rates were estimated after an overnight fast by the primed injection, continuous infusion of isotopically labeled alanine and glucose. Glucose production (mean ± SE) was 36.4 ± 2.8 mg/kg/hr (normal 129.0 ± 10.1 mg/kg/hr, n = 6). Glucose production from alanine was 3.1 ± 0.7 mg/kg/hr (normal 18.0 ± 1.0 mg/kg/hr). Alanine turnover was 241 ± 11 μmoles/kg/hr (normal 488 ± 48 μmoles/kg/hr). These data suggest that an inadequate delivery of an important gluconeogenic substrate, alanine, can exert a significant rate limitation of glucose production, thereby resulting in hypoglycemia during fasting.