Three-dimensional iterative reconstruction of high-resolution, circular orbit cone-beam x-ray CT data is often considered impractical due to the demand for vast amounts of computer cycles and associated memory. In this paper, we show that the computational burden can be reduced by limiting the reconstruction to a small, well-defined portion of the image volume. We first discuss using the support region defined by the set of voxels covered by all of the projection views. We then present a data-driven preprocessing technique called focus of attention that heuristically separates both image and projection data into object and background before reconstruction, thereby further reducing the reconstruction region of interest. We present experimental results for both methods based on mouse data and a parallelized implementation of the SIRT algorithm. The computational savings associated with the support region are substantial. However, the results for focus of attention are even more impressive in that only about one quarter of the computer cycles and memory are needed compared with reconstruction of the entire image volume. The image quality is not compromised by either method.