Because fluorine-18 fluorodeoxyglucose (18F-FDG) is an excellent tumor-localizing radio-pharmaceutical, a hand-held radiation detection probe capable of localizing an area with high 18F-FDG uptake would make radioguided surgery possible. In this laboratory study, we investigated the capability of a widely used intraoperative gamma probe with a cadmium zinc telluride (CdZnTe) detector for detection of 18F-FDG. For sensitivity tests, an 0.1- ml 18F-FDG preparation was made to act as a point source with radioactivities of 1.0, 2.0, and 3.0micro Ci (37 kBq, 74 kBq, 111 kBq). Relative transmission across the side wall of the probe and sensitivity at each source-to-probe distance were measured. For simulation studies, 2 l of 18F-FDG solution (0.02micro Ci, 0.74 kBq/ml) served as normal background. One ml of 18F-FDG was prepared to simulate tumors with radioactivities of 0.05, 0.1, 0.2, and 0.4micro Ci (1.85 kBq, 3.7 kBq, 17.4 kBq, and 14.8 kBq). The ratios of the radioactive concentration of tumor to that of the background were 2.5, 5, 10, and 20:1, respectively. The tested gamma probe was shown to be sensitive to 18F. The high-energy annihilation radiation was detected from the side wall of the probe despite application of a supplementary collimator. The count rate decreased markedly as the source-to-probe distance increased, owing to the effects of the inverse-square law. In the simulation studies, the probe detected a considerable amount of background activity. However, the measured count rate increased with the increasing source-to-background ratio. In our setting, the probe was capable of distinguishing the 18F-FDG source from the background when the source-to-background ratio was no less than 5:1. To make a surgical application feasible, however, collimation or shielding against high background radiation is necessary.