Healthy volunteers of ideal weight (12 men and 12 women) were fasted for 6 days, and obese but otherwise healthy subjects (20 men, 28 women) for 6--28 days. In all groups studied a significant increase in urinary nitrogen loss from day 1 to day 3 of fasting was followed by a steady decrease. The early rise in urinary nitrogen excretion coincided with a rise in plasma glucagon levels, suggesting a relation of the latter to increased gluconeogenesis from amino acids. At equal weight greater nitrogen losses were found in men than in women, in both normal and obese subjects. In spite of much higher weight and larger energy expenditure and nitrogen loss in obese subjects however was not higher than in normal ones. Mean daily nitrogen losses varied from 14.5 g (normal and obese men early in starvation) to 3.0 g (obese women after a 4-weeks fast). Calculating the amount of calories derived from body protien (urinary nitrogen X 6.25 X 4.1)and taking total energy expenditure from tabular metabolic values, the contribution of protein to total calorie output was found to vary from 15% (normal men 6 day fast) to 5(obese women, 4th week of fasting). The clinical significance of nitrogen loss during therapeutic fasting is discussed.