To determine the potential of Tc-99m MIBI for detecting bone marrow malignancy, MIBI imaging of the femur was evaluated. There was no detectable MIBI activity in 125 of 141 (89%) control patients. Clearly demonstrated focal or tubular MIBI activity indicating intramedullary accumulation was demonstrated in 44 of 45 (98%) patients with proven marrow malignancy: 9 patients with multiple myeloma, 10 patients with malignant lymphoma, 11 patients with acute leukemia, 1 patient with chronic leukemia, and 14 patients with skeletal metastases. No abnormal MIBI activity was observed in the femur in 19 of 22 (86%) patients who had no evidence of malignant involvement in the femoral marrow, in 3 patients with solitary plasmacytomas of the spine, sternum or iliac bone, or in 16 patients with malignant lymphoma. In 12 of 24 patients with acute leukemia in complete remission, no abnormal MIBI accumulation was shown in the femur, but in 12 patients, abnormal accumulation indicating residual leukemic activity was demonstrated. MIBI imaging correlated extremely well with MRI studies; 26 of 28 patients with focal or tubular increased MIBI activity in the femur showed decreased signal on T1-weighted images and a high signal on short inversion recovery images, and 11 patients with no abnormal activity showed a high signal on T1 images. MIBI imaging of the femoral bone marrow may be a new modality for detecting marrow malignancy.