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Correction of hepatic failure or metabolic disease by hepatocellular transplantation may require replacement of up to 10% of enzyme function with normal or genetically corrected cells. Although single injections of hepatocytes have not been able to consistently achieve this level of functional replacement in experimental models, multiple injections should theoretically be able to approach this goal. Delivery of multiple doses of hepatocytes to the spleen in experimental animals is complicated by the need to perform multiple laparotomies. By relocating the spleen to a subcutaneous position, the authors have designed an animal model to facilitate multiple splenic injections without the need for repeated celiotomies. Because it is in the prefascial plane, multiple hepatocyte injections can be delivered to the spleen percutaneously using only minimal sedation. Bleeding secondary to needle puncture is contained by a pseudocapsule which develops around the spleen. No statistical difference in the degree of hepatocyte migration to the liver has been demonstrated in animals transplanted via the subcutaneous spleen compared with animals transplanted by laparotomy (0.51% vs. 0.56%, p = .785).