Recently, we described a new solution, Carolina rinse, that prevents nonparenchymal cell injury in vitro after reperfusion of livers stored in University of Wisconsin cold solution (Currin RT, Toole JG, Thurman RG, Lemasters JJ. Transplantation 1990; 50: 1076). The present study was designed to examine the effect of Carolina rinse on graft survival in vivo. Unlike UW cold storage solution, which is high in potassium, Carolina rinse contains extracellular inorganic ions at levels similar to blood, a calcium channel blocker and a radical scavenger. Carolina rinse also contains fructose and mildly acidotic pH to reduce hypoxic cell death. Livers from Lewis rats were explanted, stored in UW cold storage solution under nonsurvival conditions, and rinsed with either 15 ml of Ringer's, UW solution, Carolina rinse, or Carolina rinse saturated with nitrogen prior to completion of implantation surgery. In the Ringer's rinse group, only 4% of recipients survived 30 days postop-eratively. In this group, SGOT levels reached maximal values of about 5000 U/L. Survival was also poor (25%) when grafts were rinsed with UW solution. In the Carolina rinse group, however, 9 of 16 rats (56%) survived indefinitely, and maximal postoperative SGOT levels were reduced 3-fold. Liver injury indexed histologically was also decreased about 3-fold by Carolina rinse compared with the control group rinsed with Ringer's solution. Carolina rinse diminished postoperative sinusoidal endothelial cell damage assessed by electron microscopy and reduced carbon particle phagocytosis due to Kupffer cells significantly. Moreover, Carolina rinse diminished graft swelling and improved postoperative hepatic microcirculation compared with the Ringer's rinse group. Taken together, these results indicate that Carolina rinse is a superior alternative to Ringer's solution in vivo to protect liver grafts from reperfusion injury when removing high-potassium-containing cold storage solutions clinically prior to implantation.