The present study was designed to determine whether the ontogenic changes in the salvage pathway for DNA synthesis of suckling rat intestine could be causally related to physiologic events during the weaning period. The intestinal activity of soluble thymidine kinase, extremely low in young sucklings (d 11, 0.057 ± 0.007 nmolmin−1·g tissue−1), increased dramatically between d 18 and 22 postpartum and reached a plateau (19.8 ± 0.5 nmol · min−1·g tissue−1) at the fourth postnatal week. Rat pups prevented from weaning showed an initial rise in the enzyme synthesis by d 18 as did their littermates weaned onto an adult diet. Compared with 22-d-old rats weaned onto chow pellets (14.1 ± 2.1 nmol · min” g tissue”), thymidine kinase concentration was reduced by one-half in rats of the same age, fed on mother's milk alone (6.5 ) 0.7 nmolmin”g tissue”) or on a liquid artificial diet either high in fat (mimicking rat milk, 7.4 ± 0.6 nmol · min” · g tissue ˜ ') or high in carbohydrate mimicking chow, 6.4 ±1.3 nmol min” g tissue”). The relative proportions of fat and carbohydrate in the diet had little or not effect on growth rate, intestinal wt, and DNA content per centimeter. In a second experiment, 9-d-old sucklings were treated for four consecutive d with either saline or hydrocortisone hemisuccinate at doses assumed to be in the physiologic (0.5 mg/100 g body wt per day) and pharmacologic (2.0 mg/100 g body wt per day) range. Low doses of the steroid failed to enhance precociously the intestinal synthesis of the enzyme and produced significant decreases in intestinal protein (-19% versus controls, P<0.05) and DNA content (—23%, P<0.01). In the jejunum as well in the ileum, the incorporation rates of pH]thymidine into DNA were reduced to a level about 70% of the controls (P=0.05). Higher doses of hydrocortisone had a marked suppressive effect on DNA synthesis in the jejunum and ileum, the values in the steroid-treated group being about one-half those of the control group.