Collagen degradation is essentially the only source of free and peptide hydroxyproline in plasma and urine. Normally over 95% of the hydroxyproline in urine is peptide-bound, and the excretion of peptide hydroxyproline has been used to follow collagen metabolism. Newborn infants 1–2 wk old excreted about 60 times more free hydroxyproline per kg than infants 6–12 months old. The excretion of hydroxyproline peptides per kg in the young infants was only slightly greater than the hydroxyproline peptide excretion in the older infants, suggesting that changes in collagen catabolism cannot be a major factor in explaining the large excretion of free hydroxyproline in young infants. In fullterm infants the ratio of free to peptide hydroxyproline in urine appeared to increase during the first few days of life, and then it gradually decreased to adult levels in about 5 months. The ratio of free to peptide hydroxyproline in urine was even higher in premature infants, and it remained high longer than in full-term infants. Plasma levels of free hydroxyproline were higher in the young infants than in old infants, suggesting that changes in renal function could not in themselves explain the large excretion of free hydroxyproline. Measurements of plasma levels and excretion rates following an oral load of hydroxyproline indicated that the catabolism of free hydroxyproline is impaired in early infancy. Hydroxyproline oxidase activity in liver homogenates from fetal and newborn rats was only about one third the activity of adult rats, and the oxidase activity developed slowly in the first 10 days of life.