Administration of dexamethasone, 8 mg/day (0.02 mmol/day), for 5 days to normal subjects produced negative N2 balance, due to early and sustained increases in urinary urea N2 excretion. In 8 subjects ingesting 0.9-1.6 g of protein day-1 kg-1 body wt the cumulative increment in urea N2 excretion averaged +12.5 g (SEM [standard error of the mean] 2.8, P < 0.01) over 5 days of glucocorticoid administration. Increases in urinary urea N2 excretion could be related to plasma alanine and blood glutamine changes by using a multiple regression equation. Corticosteroids may induce increased release of alanine and glutamine by peripheral tissues, which may augment urea formation and negative N2 balance. The correlation between increments in urea N2 excretion and increases in plasma arginine remains unexplained.