As a preface to studies on the feasibility of liver segment transplantation, we studied the course of liver regeneration in immunosuppressed rats. Partial hepatectomies were performed in young adult male rats who were then treated with daily cyclosporine, dexamethasone, the combination of both agents, or vehicle. Body weight, liver weight, and liver DNA content were measured in subgroups of rats studied at various times after partial hepatectomy. All treated animals experienced weight loss, a phenomenon most marked in animals treated with both dexamethasone and cyclosporine. The DNA content of regenerating liver increased initially after partial hepatectomy in all animals. Restoring their original hepatic DNA in a fashion indistinguishable from controls, animals treated with cyclosporine increased liver DNA four fold within the first six days after partial hepatectomy. Animals treated with dexamethasone and both dexamethasone and cyclosporine increased their complement of liver DNA 2.5 fold, to 80% of that originally present. After day 6, the combined cyclosporine and dexamethasone treatment group became extremely catabolic and experienced a sharp decline in liver DNA. We conclude that despite the deleterious effects of cyclosporine and dexamethasone, especially in combination, on weight gain following partial hepatectomy, these agents do not prevent DNA synthesis and the accretion of new liver mass. We are encouraged by these studies to proceed with experimental studies on the normal growth and repair of liver segments transplanted into an immunosuppressed host.