UNLABELLED The present study evaluated the role of SPECT/CT as an adjunct to (67)Ga (GS) or (111)In-labeled white blood cell (WBC) scintigraphy for diagnosis or localization of infection. METHODS Eighty-two patients (56 male and 26 female; mean age, 62 y) assessed for known or suspected infectious processes underwent 88 SPECT/CT studies. Forty-seven patients underwent GS SPECT/CT (13 with fever of unknown origin, 21 with suspected osteomyelitis, and 13 with suspected soft-tissue infection), and 35 patients underwent WBC SPECT/CT (24 with suspected vascular graft infection, and 11 with suspected osteomyelitis). Ninety-eight suggestive sites were identified (52 on GS and 46 on WBC). Additional information provided by SPECT/CT for diagnosis or localization of infection, as compared with planar and SPECT scintigraphy, was recorded. The SPECT/CT contribution was analyzed on a patient and site basis and was compared for the 2 tracers and clinical indications. RESULTS SPECT/CT provided additional information for infection diagnosis and localization in 39 (48%) of 82 patients and in 47 (48%) of 98 sites. SPECT/CT defined the extent of infection in 35 patients (43%) in 43 sites (44%) and excluded infection in 4 suggestive sites defined as physiologic bowel uptake on GS. SPECT/CT was incorrect in 2 suggestive sites (1 GS and 1 WBC). The contribution of SPECT/CT was significantly higher for WBC than for GS (P < 0.05)--in 63% versus 36% of patients, respectively, and in 61% versus 36% of sites, respectively. CONCLUSION SPECT/CT made an incremental contribution to GS and WBC in 48% of patients with suspected infections, by improving diagnosis, localization, and definition of extent of disease. SPECT/CT has an important role mainly with highly specific, low-background infection-seeking tracers such as WBC.