For many hematological malignancies, high-dose chemoradiotherapy followed by bone marrow transplantation offers the best and sometimes the only chance for cure. However, the main causes of failure of this therapy are relapse and toxicity. In order to selectively deliver higher doses of radiotherapy to the bone marrow and to spare normal organs, we explored 52Fe therapy before a conventional BMT conditioning regimen. Twenty-four patients at high risk for relapse after BMT were included in a phase II study. The median follow-up was 42 months. The median 52Fe dose was 59 mCi. This resulted in a median radiation-absorbed dose (RAD) to the BM of 626 rad. The median RAD to the liver was 338 rad. No untoward effects were noted after the injections of 52Fe. The patients recovered hematopoiesis without toxicity in excess of that expected with conventional conditioning alone. The 3-year DFS probability was 49% (95% CI: 20-78%). Eight patients have relapsed, three of them in extramedullary sites. 52Fe should provide a way to boost the radiation dose to marrow-based diseases before bone marrow transplantation without excessive toxicity.