The changes in the content of STH and FFA in the blood and of catecholamines in the urine under the effect of insulin hypoglycemia were studied in 28 insulin-sensitive and 40 insulin-resistant patients suffering from diabetes mellitus. Patients with diabetes mellitus who needed 100 or more insulin units per 24 hours for compensation of the affection were referred to the insulin-resistant ones. In these cases a less pronounced elevation of the blood STH level and of urinary catecholamines was noted in response to insulin hypoglycemia. This was accompanied by a considerable reduction of lipolysis in the insulin-resistant patients. It is suggested that in the insulin-resistant patients, due to reduction of the STH and catecholamine stimuli, FFA is incapable of providing the necessary energy balance at the cellular level in insulin insufficiency. This accounts for an increased requirement in exogenous insulin in the insulin-resistant patients with diabetes mellitus. Reduction of the FFA and catecholamine reserves in the insulin-resistant patients suffering from diabetes mellitus is postulated to be one of the main factors in the resistance pathogenesis.