Total parenteral nutrition (TPN) decreases disaccharidase activity in the small intestine of humans and miniature piglets. The possibility, however, that specific components of TPN (eg, the energy mix) will increase disaccharidase activity has largely been unexplored. The identification of such components would be particularly useful in the treatment of premature infants with immature gastrointestinal tracts and patients with small intestinal mucosal disease associated with decreased disaccharidase activity. To determine whether the TPN energy composition affects small intestinal disaccharidase activity, 7-day-old miniature piglet littermates were randomized to receive TPN containing either glucose (group G) or glucose and fat (group G/F) as the nonnitrogen energy source(s). The TPN regimens were isonitrogenous and isoenergetic. The piglets were not allowed oral intake during the 7 days they were maintained on TPN. At 14 days of age the piglets were killed and the small intestines analyzed for weight, protein, DNA, and disaccharidase activity. Body weight was similar between groups at both the beginning and end of the study. The TPN regimen did not affect small intestinal weight of protein and DNA content. However, jejunal and ileal sucrase and ileal maltase activities (mumol/min.kg body wt +/- SD) were greater in group G than those in group G/F (28 +/- 9 vs 19 +/- 11, p = 0.04; 13 +/- 7 vs 7 +/- 4, p = 0.037; and 31 +/- 8 vs 19 +/- 10, p = 0.0088, respectively). No differences in lactase activity were noted between groups.(ABSTRACT TRUNCATED AT 250 WORDS)