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We have developed a dual-modality CT/SPECT imaging system for small-animal imaging applications. The X-ray system comprises a commercially available micro-focus X-ray tube and a CCD-based X-ray camera. X-ray transmission measurements are performed based on cone-beam geometry. Individual projections are acquired by rotating the animal about a vertical axis in front of the CCD detector. A high-resolution CT image is obtained after reconstruction using an ordered subsets-expectation maximization (OS-EM) reconstruction algorithm. The SPECT system utilizes a compact semiconductor camera module previously developed in our group. The module is mounted perpendicular to the X-ray tube/CCD combination. It consists of a 64 × 64 pixellated CdZnTe detector and a parallel-hole tungsten collimator. The field of view is 1 square inch. Planar projections for SPECT reconstruction are obtained by rotating the animal in front of the detector. Gamma-ray and X-ray images are presented of phantoms and mice. Procedures for merging the anatomical and functional images are discussed.