On the basis of observations in patients with long-term (28–30 years) renal allograft survival, all of whom had evidence of systemic microchimerism, we began a program of combined simultaneous kidney/bone marrow transplantation. Between 12/14/92, and 10/31/94, 36 kidney transplant recipients received 3–5 × 108 unmodified bone marrow cells/kg; 6 patients also received pancreatic islets, and 7 patients also received a pancreas. The mean recipient age was 39.0 ± 10.8 years, and the mean donor age was 31.8 ± 16.1 years; the mean cold ischemia time was 23.0 ± 9.1 hr. Twenty control patients received kidneys alone, mainly because of refusal by the donor family to consent to vertebral body recovery; 3 of these patients also received a pancreas. The mean recipient age was 47.9 ± 11.7 years, and the mean donor age was 41.5 ± 17.9 years; the mean cold ischemia time was 28.6 ± 6.2 hr. All patients received tacrolimus-based therapy, without radiation, cytoreduction, or induction antilymphocyte preparations. Blood was drawn prior to and at regular intervals after transplantation for detection of chimerism and for immunologic studies. With a mean follow-up of 11.1 ± 5.8 months, all 36 study patients are alive, and 33 (92%) have functioning allografts with a mean serum creatinine of 1.9 ± 1.2 mg/dl and a BUN of 26 ± 9 mg/dl. Graft vs. host disease was not seen in any patient. The incidence of rejection was 72%; 11% of the patients required OKT3 or ATG for steroid-resistant rejection. The incidence of CMV was 14%, and that of delayed graft function was 17%. A total of 18 (90%) control patients are alive, and 17 (85%) have functioning allografts, with a mean serum creatinine of 2.1 ± 1.3 mg/dl, and a BUN of 30 ± 13 mg/dl. The incidence of rejection was 60%, and 10% required OKT3 or ATG. CMV was seen in 15%, and delayed graft function in 20% (P=NS). In the study patients, chimerism was detected in the peripheral blood of 30 of 31 (97%) evaluable patients by either PCR or flow cytometry. In the control patients, chimerism was seen in 9 of 14 (64%) evaluable patients (P<.02). Decreasing donor-specific responsiveness was seen in 6/29 (21%) evaluable study, and 4/14 (29%) evaluable control patients (P=NS). We conclude that combined kidney/bone marrow transplantation is associated with acceptable patient and graft survival, augmentation of chimerism, and no change in the early events after transplantation.