Corticosteroids result in protein wasting in human adults and rats. To determine to what extent this therapy affects protein metabolism in preterm infants, we studied 10 very low birth weight infants before a gradually tapered dexamethasone regimen was started and at day 4 of treatment (dexamethasone dosage 0.35 +/- 0.09 mg.kg-1.day-1), and seven infants at day 19 of treatment (dexamethasone dosage, 0.10 +/- 0.01 mg.kg-1.day-1). Protein breakdown and turnover rates were increased at day 4 of treatment but not any more at day 19 of treatment. Protein synthesis rate was not significantly affected during dexamethasone therapy. Weight gain was severely diminished during the first week of treatment but not during the next 2 weeks. We conclude that nitrogen balance during high dosages of dexamethasone is significantly lower because of an increase in proteolysis and not because of a suppression of synthesis.