Delayed hematologic recovery is common after unrelated donor umbilical cord blood transplants (UCBT). Clinically it is important to quickly differentiate slow engraftment from graft failure (GF). We report the engraftment data on 110 pediatric UCBT recipients. By day 28, 71 patients achieved an ANC >0.5 x 10(9) per liter, and 6 others died early without recovery. Of the remaining 33 patients who were still neutropenic, 20 eventually attained donor myeloid recovery, 3 died of transplant-related complications or recurrent leukemia and 10 survived without donor-derived hematopoiesis. These patients received a second UCBT 33-95 days after the first transplant, after additional immunosuppression. One patient died early, the remaining nine patients were engrafted; eight demonstrated complete, and one mixed, donor chimerism (with subsequent graft loss). Acute GVHD developed in three, and chronic GVHD in six of the eight engrafted patients. Two patients developed EBV-lymphoproliferative disorder. Infections, especially viral, were common and protracted. Six of 10 patients are alive, 165-1375 (median 1147) days after second UCBT. Chimerism studies correlated with subsequent engraftment course. Any result showing <5% donor cells was associated with irreversible graft loss. In conclusion, early second UCBT after primary GF is a feasible treatment option. Chronic GVHD and viral reactivation are common post transplant.