Bacterial translocation (BT) of enteric organisms is a major cause of sepsis in patients undergoing small bowel transplantation (SBT). Cyclosporine (CsA) may be toxic to intestinal epithelium and increase the risk of BT. Glutamine (Gln) is the preferred enterocyte fuel and maintains graft epithelial integrity in experimental SBT. This study determined the effects of CsA on mucosal structure and function of transplanted intestinal isograft and examined whether Gin-enriched diet reversed CsA-induced intestinal toxicity. Thirty-three adult Lewis rats underwent resection of the distal 60% of small bowel and received an orthotopic jejunal isograft. Rats received either elemental diet with 2% Gin or the same diet with balanced nonessential amino acids (non-Gin) by gastrostomy for 10 days. CsA (15 mg/kg, im) or olive oil was injected daily. Rats were assigned to four groups: non-Gin with vehicle, non-Gin with CsA, Gin with vehicle, and Gin with CsA. Mucosal villous height, surface area, crypt depth, C-14 glucose absorption, BT to mesenteric lymph nodes (MLN), and body weight change were evaluated. The non-Gin with CsA group had the highest incidence of BT (P < 0.001). Gin groups had significantly decreased BT (P < 0.01) and increased crypt depth and villous surface area (P < 0.01) when compared to non-Gin groups. Body weight significantly decreased in CsA groups when compared to non-CsA groups (P < 0.01). These results indicate that CsA significantly decreased body weight and increased BT without decreasing mucosal structure and glucose absorption of intestinal isografts. Gin significantly reduced the incidence of BT to MLN and improved mucosal structure in CsA and non-CsA groups. (C) 1995 Academic Press, Inc.