In medical practice today, diabetic ketoacidosis results in a fatal outcome for 10% of patients, and in the hyperosmolar non-ketoacidosis syndrome 50% die. Thrombotic complications account for a considerable proportion of the deaths of these patients and cerebral manifestations are characteristic of their hyperosmolar state. A strategy which leads to improved management and survival of these severely decompensated patients remains to be found. Recommendations for management of these patients are presently controversial because the aetiology of their cerebral disturbance is ill-defined. This thesis describes novel alterations in blood from patients with ketoacidosis which are particularly associated with the development of the hyperosmolar state. The combination of these abnormalities with other factors present, leads to an unique summated effect on the flow properties of blood during severe diabetic decomposition. Subsequently impaired perfusion could therefore account for the depressed conscious level, strokes and fatal thrombotic phenomena commonly associated with diabetic ketoacidosis. The biochemical alterations underlying the blood abnormalities were studied both in humans and in animals with severe diabetic ketoacidosis. The findings which emerged from the study are particularly relevant to planning treatment and monitoring the pathophysiological response of vital tissue in these patients. It is possible that we can reduce the mortality of these serious medical conditions and improve the outlook for the diabetic individual if we elucidate the underlying pathophysiological changes and adjust treatment accordingly.