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 nmol X min-1 X g tissue-1), increased dramatically between d 18 and 22 postpartum and reached a plateau (19.8 +/- 0.5 nmol X min-1 X 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 X min-1 g tissue-1), thymidine kinase concentration was reduced by one-half in rats of the same age, fed on mother's milk alone (6.5 +/- 0.7 nmol X min-1 X g tissue-1) or on a liquid artificial diet either high in fat (mimicking rat milk, 7.4 +/- 0.6 nmol X min-1 X g tissue-1) or high in carbohydrate mimicking chow, 6.4 +/- 1.3 nmol X min-1 X g tissue-1). 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.(ABSTRACT TRUNCATED AT 250 WORDS)