Cyclosporine A was withdrawn from a triple drug immunosuppressive regimen in 10 clinically and biochemically stable liver transplant patients. This study reports the effects of cyclosporine A withdrawal on liver tests and liver histology. Serum aspartate amino transferase and serum alanine amino transferase values increased significantly. Seven out of ten patients had histological changes after cyclosporine A withdrawal, but not before. These changes were compatible with acute rejection (consistent with rejection) in two patients and grade I also in two patients, including one patient with a second graft. Only two of these patients needed corticosteroid treatment (one consistent with rejection and one grade I rejection). Cyclosporine A treatment was restarted in three patients, because a coexisting osteoporosis prohibited prolonged corticosteroid recycling. Seven patients were able to maintain stable though slightly elevated transaminases without cyclosporine A, with a follow up of median 26 months. Our results suggest that in stable patients cyclosporine A withdrawal can be considered, for instance 2 years after liver transplantation.