The histology of rat small bowel transplants (SBT) was examined in orthotopic isografts and allografts with and without immunosuppression. Lewis to Lewis isografts were examined 7 days after transplant, and LBNF1 to Lewis allografts were examined 2, 4, 7, and 10 days after transplant; one group received cyclosporine A (CyA), and their allografts were examined 7 days after transplant. Compared with similar intestinal segments from unoperated animals, allografts at 4, 7, and 10 days after surgery showed progressive inflammation, cryptitis, villous atrophy, and transmural necrosis. In contrast, SBT in animals given CyA did not significantly differ from normal in any histological parameter. The number of apoptotic structures per 100 crypts in SBT at day 4 (58.25 ± 32.98) and day 7 (31.86 ± 27.63) after transplant were significantly increased compared with unoperated bowel (5.23 ± 13.41) ( P < .05); the number in CyA-treated allografts (11.57 ± 29.56) did not differ significantly from normal. The number of intermyenteric ganglion cells was significantly reduced ( P < .05) in allografts 7 and 10 days after transplant (mean and [range] = 31 [18 to 38] and 25 [23 to 27], respectively) but the number in allografts from CyA-treated animals (47 [24 to 72]) did not differ from unoperated bowels (52 [30 to 88]). We conclude that CyA treatment significantly reduces the histological abnormalities associated with transplant rejection including adverse effects on epithelial and ganglion cells; therefore, the absorptive capacity and motility characteristics of the CyA-treated SBT should be preserved compared with untreated allograft controls.