Diamine oxidase (DAO) is an intestinal mucosal enzyme which serves as a marker of cellular maturity and integrity in ontogeny and after mucosal injury in the gastrointestinal tract. Since total parenteral nutrition is known to result in intestinal hypoplasia, this study was done to determine the effect of enteral and parenteral delivery of nutrients on gut structure and DAO levels. Central venous catheters were placed in 27 Sprague-Dawley rats (180-260 g), which received nutrients for 12 days via parenteral nutrition (GpI n = 10), oral intake of the parenteral solution (GpII n = 8), or standard rat chow (GpIII n = 9). Gross and microscopic measurements were made at sacrifice. Mucosal DAO levels were determined by metabolism of [3H] putrescine. Group III animals had a greater caloric intake than groups I and II, and were the only group with a significant increase in body weight. Gut weight, mucosal weight, and villous height were significantly less in group I vs groups II and III; group II values were less than group III (p less than 0.05). Both DAO specific activity and total gut DAO were significantly less in group I and group II. Mucosal DAO content correlated with total gut and mucosal weight. DAO mucosal levels decrease with parenteral nutrition, reflecting the intestinal hypoplasia that occurs. Mucosal DAO content may be dependent on both caloric intake and diet composition. Since serum DAO levels are known to correlate with mucosal DAO content, DAO activity may prove useful as a circulating marker of the effect of nutritional therapy on the intestinal mucosa.