Fifteen end-stage renal disease patients with high titres of panel reactive (PRA) antibodies were treated with immunoadsorption (IA) on sepharose-bound protein A columns in order to remove anti-HLA antibodies and facilitate transplantation. Infectious complications were not observed after IA and transplantation, and the procedure was well tolerated. In spite of the use of adjunctive immunosuppressive treatment with cyclophosphamide and prednisolone, this method produced only variable effects in lowering panel reaction antibodies, and was hampered by high de novo resynthesis of anti-HLA antibodies. Patients whose pre-IA antibody titre was greater than or equal to 1:64 clearly did not benefit from the procedure, but other immunological criteria were not predictive of efficacy. Twelve patients were transplanted on the basis of a negative cross-match with current serum, historical sera being retrospectively tested. Surprisingly, seven patients received a well-matched graft with both pre- and post-IA negative cross-matching. Graft survival was 86% in this group. Conversely, in the group of five transplants which were performed in recipients having a positive historical cross-match with the donor, graft survival was only 40%. One patient died with a functional graft, and two grafts failed due to hyperacute humoral rejection. Humoral rejection in a third patient was successfully treated by a second IA course and administration of polyclonal IgG. We conclude that IA is a safe procedure for managing hyperimmunized transplant candidates. However, its efficacy remains variable, and a better definition of patients who should benefit from IA needs to be found.