Although photon deficient defects on bone scan have received a great deal of interest, such defects in bones on Indium-111 (111In) leukocyte imaging have not been as well recognized. We therefore undertook a retrospective review to determine the frequency and significance of such "cold" defects on 111In-labeled leukocyte imaging. Three hundred thirty-two scans on 290 patients were reviewed and 40 cases of decreased activity involving bone were found, for an incidence of 12%. The causes of the defects were: fracture (eight), nontraumatic avascular necrosis (eight), solid tumor (six), prostheses and other orthopedic hardware (four), advanced age (four), radiation (three), leukemia (two), osteomyelitis (two), myelofibrosis (one), postlaminectomy (one), and idiopathic (one). To determine the frequency of cold defects in osteomyelitis, all 15 cases of osteomyelitis in this series were reviewed and 12 showed increased activity, two were cold, and one was normoactive. Thus, 14% of cases of osteomyelitis presented as cold defects. We conclude that cold bone defects do occur on 111In-labeled leukocyte scans and that the causes of such defects are similar to those reported for bone and bone marrow scanning.