Immunoscintigraphy with technetium-99m labelled anti-granulocyte antibodies (AGA) is an equivalent technique to imaging with in vitro-labelled leucocytes, which is now considered state of the art in the diagnostic work-up of patients with suspected post-traumatic chronic osteomyelitis. In this study, we evaluated the use of a combined single-photon emission tomography/computed tomography (SPET/CT) device to improve detection and anatomical definition of inflammatory bone lesions. Twenty-seven patients with 29 sites of suspected bone infection underwent immunoscintigraphy with 750 MBq 99mTc-labelled AGA. Planar scans were acquired immediately, 4 h and 24 h after injection, and combined SPET/CT was performed using a dual-head multifunctional gamma camera equipped with a low-power X-ray system. Accumulation of AGA in inflammatory lesions was quantitated, comparing uptake at 4 and 24 h after injection. The validation was based on culture data derived from surgical or biopsy samples (20 lesions in 18 patients) or clinical follow-up without further therapy for more than 6 months (nine lesions). On a lesion-by-lesion basis 19 true positive, one false positive and nine true negative findings were obtained. SPET/CT correctly identified the location of all positive foci in the appendicular skeleton and that of a cold lesion in the axial skeleton. It also enabled differentiation between soft tissue infection, septic arthritis and osteomyelitis, as well as between cortical, corticomedullary and subperiosteal foci. Sensitivity was identical for SPET and SPET/CT (100%), whereas specificity was improved from 78% to 89% by the use of SPET/CT. Combined SPET/CT improves the accuracy of immunoscintigraphy by allowing correct differentiation between soft tissue infection and bone involvement. This technique may gain clinical relevance in the selection of patients for surgical therapy.