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The authors have developed a multimodality system for imaging the biodistribution of biologically interesting ligands tagged with 125I. By incorporating a small fluoroscope as an additional modality, they have enhanced their small animal nuclear imaging system to include both X-rays and images from two Hamamatsu R3292 5" diameter position sensitive photomultiplier tubes (PSPMT) viewing pixelated scintillators with image co-registration of 1.5 mm or better. Collimators placed between the animal and the scintillators can easily be interchanged and include CuBe parallel-hole collimators with a range of resolution and sensitivity combinations. The small X-ray fluoroscope provides 5 cm diameter images, several of which can readily be combined to provide structural anatomical information from the animal under study. The system has been tested by comparing the uptake of 125I (in NaI) in control mice and mice previously fed a solution of KI (potassium iodide) designed specifically to block uptake of the radiolabeled iodine in the thyroid. This system not only provides an effective approach for the analysis of KI dose and toxicity issues but also allows for detection of individual variation in animals, an important issue in contemporary pharmacology and genomics.