The influence of body water and solute equilibria between extracellular fluid and cerebrospinal fluid (CSF), both before and during therapy, was studied in fifty-three patients who had hyper-glycemia (blood glucose 600 mg./100 ml.) in the absence of ketoacidosis. Particular attention was directed to both depression of sensorium and the possible production of cerebral edema. Before therapy, depression of sensorium was highly correlated with plasma osmolality (r =.84), but not with glucose concentration or pH of either CSF or plasma. Plasma and CSF were in osmotic equilibrium before therapy (389 mOsm/kg.) but glucose concentration was significantly higher in plasma while Na+ and Cl− were higher in CSF. During treatment with insulin and hypotonic NaCl infusion, the osmolalities of CSF and plasma fell at essentially identical rates. Plasma osmolality fell as a consequence of both a fall in glucose concentration and a gain in free water, but the fall in CSF osmolality was almost entirely due to a gain in water by the CSF. Insulin administration was stopped when plasma glucose was about 250 mg./100 ml., and in all patients there was no increase in CSF pressure or clinical evidence of cerebral edema. In patients with nonketotic coma, depression of sensorium is highly correlated with the plasma osmolality. During therapy with insulin and hypotonic NaCl infusion, it appears that cerebral edema does not occur if insulin is stopped before plasma glucose falls below 250 mg./100 ml.