The effects of nitric oxide (NO) during small bowel preservation and reperfusion were studied in a rat model of heterotopic, syngeneic LEW-->LEW transplantation. A 6-hr preservation interval was chosen, which leads consistently to moderate graft injury permitting graft and recipient survival. To evaluate the function of NO during preservation and reperfusion, two inhibitors (NitroG-L-arginine methyl ester [L-NAME] and NG-monomethyl-L-arginine [NMA]) were administered and compared with a transplanted group receiving no treatment. The extent of preservation and reperfusion injury were delineated by histologic study and by the measurement of mucosal glutaminase on tissue specimens obtained 20 min after revascularization and 24 hr and 4 weeks postoperatively. Serum and mucosal NO(2-)+NO3- levels were determined at the same time points. Graft function and survival was inferior in all cases where NO production was inhibited. When recipients were treated with NO inhibitors, graft function and survival was more impaired when L-NAME was administered compared with NMA administration. Donor and graft pretreatment with NO inhibitors impaired graft function but not survival, and was less detrimental than recipient treatment. Mucosal NO(2-)+NO3- levels significantly increased in untreated transplanted animals 20 min after reperfusion. This increase was abolished in groups treated with NO inhibitors. Serum NO(2-)+NO3- levels increased significantly after 24 hr, and this increase was even more pronounced when NO inhibitors were administered. Furthermore, liver function deteriorated after inhibition of NO, indicating a more severe inflammatory response of the recipient after NO inhibition. These data indicate that mucosal NO production within the graft during preservation, and especially during reperfusion, has beneficial effects, but increased serum NO(2-)+NO3- levels coincided with inferior graft condition due to preservation and reperfusion injury.