Transplantation of histocompatible allogeneic peripheral blood leukocytes resulted in successful reconstitution of an adenosine deaminase (ADA)-deficient, severe combined immune-deficient patient. Erythrocyte transfusions before the transplant were associated with a rise of serum immunoglobulin concentration to normal without improvement in T cell function. The patient received 5 x 10(7) peripheral blood mononuclear leukocytes/kg obtained from the histocompatible father by leukopheresis. 3 wk after the transplant the lymphocyte count, proportion of E rosetting lymphocytes, and the ADA content of the patient's mononuclear leukocytes became normal while the phytohemagglutinin-stimulated blastogenic responses improved and became normal 52 d after the transplant. Antibody response to diphtheria immunization and response to naturally acquired herpes simplex infection were normal while isohemagglutinins progressively increased. Immunization with a neoantigen, bacteriophage phiX 174, resulted in a small but definite antibody response but no amplification of the response after secondary immunization. A positive reaction to a skin test for Candida albicans developed. Erythrocyte deoxy ATP (dATP) concentration decreased during the course of erythrocyte transfusions. 9 mo after the transplant, the erythrocyte dATP was elevated to twice pretransfusion levels while mononuclear leukocyte dATP varied from normal to elevated during the first 4 mo of the posttransplant period, but remained normal during the last 8 mo. The improvement in immune function persisted during the 12-mo posttransplant observation period while the mononuclear leukocyte ADA concentration stabilized at approximately 0.25 of normal, which is similar to the enzyme activity of the donor cells. This in vivo study supports the hypothesis that lymphoid precursor cells are present in peripheral blood which may partially reconstitute an immune-deficient recipient.