Computed tomography (CT) applications continue to expand, and they require faster data acquisition speeds and improved spatial resolution. Achieving isotropic resolution, by means of cubic voxels, in combination with longitudinal coverage beyond 20 mm would represent a substantial advance in clinical CT because few commercially available scanners are capable of this at present. To achieve this goal, a prototype CT system incorporating a movable array of 20 cm X 20 cm, 200-microm-pitch amorphous silicon flat-panel x-ray detectors and a conventional CT x-ray source was constructed at the General Electric Global Research Center and performance tested at The University of Texas M. D. Anderson Cancer Center. The device was designed for preclinical imaging applications and has a scan field of 13 to 33 cm, with a magnification of 1.5. Image quality performance measurements, such as spatial and contrast resolutions, were obtained using both industry standard and custom phantoms. Spatial resolution, quantified by the system's modulation transfer function, indicated improvement by a factor of 2.5 to 5 in isotropic spatial resolution over current commercially available systems, with 10% modulation transfer function modulations at frequencies from 19 to 31 lp/cm. Low-contrast detectability results were obtained from industry-standard phantoms and were comprised of embedded contrast regions of 0.3%, 0.5%, and 1.0% over areas of several mm2. Performance was sufficient to easily distinguish 1.0% contrast regions down to 2 mm in diameter relative to the background. On the basis of scans of specialized hydroxyapatite phantoms, the system response is extremely linear (R2=0.990) in bone-equivalent density regimens. Standard CT dose index CTDI100 and CTDIw measurements were also conducted to assess dose delivery using a 16-cm-CTDI phantom and a 120 kV 120 mAs scan technique. The CTDIw ranged from 30 mGy (one-panel mode) to 113 mGy (two-panel mode) for this system. Lastly, several in vivo canine and murine samples were examined, and preliminary results from these scans are presented. On the basis of our results, it is clear that flat-panel-based CT scanners are useful for high-contrast high-resolution clinical applications, providing up to a 20-fold increase in volumetric resolution over most commercially available scanners.