Fourteen patients (16 sites) with clinical and/or radiographic evidence of neuropathic osteoarthropathy (Charcot joints) were evaluated with combined indium-111-leukocyte (111In-WBC) and technetium-99m-methylene diphosphonate (99mTc-MDP) bone imaging for suspected osteomyelitis. Magnetic resonance (MR) images were obtained in seven patients. Using a positive bone culture as the criterion for the presence of osteomyelitis, there were four true-positive studies, six true-negative sites, and one false-negative 111In-WBC study. Five of 16 sites (31%) had false-positive 111In-WBC uptake at noninfected sites. There were four true-positive and three false-positive MR studies. All false-positives showed at least moderately abnormal findings by both techniques at sites of rapidly progressing osteoarthropathy of recent onset. In this preliminary study, both techniques appear to be sensitive for detection of osteomyelitis, and a negative study makes osteomyelitis unlikely. However, the findings of 111In-WBC/99mTc-MDP and MR images at sites of rapidly progressing, noninfected neuropathic osteoarthropathy may be indistinguishable from those of osteomyelitis.