T and B cells from one short-term and nine long-term patients who had received HLA-identical bone marrow transplants for aplastic anemia or hematologic malignancy were studied for their ability to synthesize immunoglobulin after in vitro stimulation with pokeweed mitogen, Herpes simplex type 1 antigen, tetanus toxoid, or Epstein-Barr virus. Purified T, OKT4, OKT8, or B cells from patients were cocultured with normal T and/or B cells in the presence of the various stimulants. Multiple regulatory defects were observed in long-term patients with and without chronic graft-versus-host disease. The lymphocytes from the long-term healthy chimeras exhibited fewer defects in their ability to regulate in vitro immunoglobulin synthesis than those of patients with chronic graft-versus-host disease. These findings suggest that the presence of chronic graft-versus-host disease delays or impairs the "rematuration" of the immune system after bone marrow grafting and that the rematurational process occurs at the clonal level.