We compared the relative efficacy of medium- and long-chain triglycerides and dextrose on intestinal adaptation. Parenterally nourished rats received an isocaloric luminal infusion of one of these three substrates for 1 wk into either the jejunum or the ileum. Intestinal mass (mucosal weight and protein content) as well as the in vivo absorption of 5 mM glucose, valine, and aspartic acid were measured. In the jejunum, long-chain triglycerides were the most trophic, whereas in the ileum, long-chain triglycerides and dextrose were equally effective, but significantly more trophic than medium-chain triglycerides. In general, absorptive function was better maintained by dextrose and medium-chain triglycerides than long-chain triglycerides in the jejunum or by dextrose in the ileum. These data demonstrate that the jejunum and ileum respond differently to caloric substrates. Medium-chain triglycerides do not appear to have a clear superiority to long-chain triglycerides or dextrose in producing intestinal adaptation.