The effect of two isocaloric evening meals (low protein-high fat vs. high protein-low fat content) on plasma glucose regulation during the night were compared. Eight C-peptide-deficient type-I diabetic subjects without autonomic neuropathy were treated with fixed doses of continuous infusions of insulin during 2 nights. At 7 p.m. they received in random order either a low protein-high fat (5% of total energy protein, 60% fat, 35% carbohydrate) or a high protein-low fat (35% protein, 30% fat, 35% carbohydrate) evening meal. Venous plasma samples were drawn hourly thereafter. Plasma glucose concentrations were similar postprandially during the 2 nights between 7 p.m. and 11 p.m., but they were higher in the early morning hours after the high protein meal (p < 0.02 vs. the low protein meal). Two subjects developed symptomatic hypoglycemia after the low protein meal. Plasma glucagon concentrations were higher (p = 0.023) and serum free insulin lower (p < 0.05) after the high protein-low fat meal. Plasma cortisol and growth hormone were not significantly different between the two diets. Therefore, an increase in the protein content of the evening meal (fat content diminished) increases plasma glucose concentrations several hours later in the night, possibly due to protein-induced glucagon secretion and to lower plasma free insulin levels. Patients with type-I diabetes with a tendency to develop hypoglycemia during the night may avoid this problem by increasing the protein content of the evening meal.