Strontium-89 is routinely used for pain control in advanced skeletal metastatic disease. A common side effect of Sr-89 therapy is a mild to moderate bone marrow suppression. To avoid complications from marrow suppression, a pretreatment platelet count of > 60,000/mm3 and a WBC count of > 2,400/mm3 are suggested. The authors present two patients who, despite satisfying these criteria, developed profound and prolonged bone marrow suppression after therapy. The severity of this response was most likely caused by pre-existing extensive bone marrow replacement with tumor. The contribution of local radiation therapy to bone marrow suppression is presumed to be minimal. The authors recommend that pretreatment criteria for determination of eligibility for Sr-89 therapy in selected patients be expanded to include steadily decreasing blood counts, and evaluation of extent of marrow involvement by biopsy or MR imaging.