Total parenteral nutrition (TPN) is widely used in premature and/or surgical neonates, but there is little information available about its effects on intestinal growth and development. Adult TPN models have demonstrated mucosal atrophy, and a young piglet model showed similar but increased intestinal hypotrophy. We have investigated these effects in the neonatal piglet model. Five three-day old piglets received a glucose (40 g/kg/d), amino acid (8 g/kg/d), and fat (4 g/kg/d) solution intravenously for 3 weeks. Matched littermates were fed an artificial sow-milk formula enterally at an equivalent caloric rate (215 kcal/kg/d). A third littermate was sow breast fed for the same study period. No differences were seen in the TPN or formula-fed piglets in weight gain (31 to 34 g/kg/d), hematocrit (25% to 27%), BUN (12 to 13 mg/dL), total serum protein (4.1 to 4.4 g/dL), or total bilirubin (0.4 to 0.6 mg/dL); however, the TPN animals were mildly hyperglycemic (167 mg/dL). The sow-fed control group had greater weight gain (51 g/kg/d) but were without caloric restriction. There were significant decreases in weight and length of the gastrointestinal tract, particularly in the proximal small bowel of the TPN piglets. Compared with formula piglets or sow-fed controls, the TPN proximal small bowel weight was reduced by 67% and 72%, respectively. Similar but less marked differences were seen in the TPN distal small bowel. There were no significant differences in the proximal or distal small bowel measurements between the formula and sow-fed piglets, despite their differences in overall weight gain.(ABSTRACT TRUNCATED AT 250 WORDS)