For patient setup verification in external beam radiotherapy (EBRT) of prostate cancer, we developed an information theoretic registration framework, called the minimax entropy registration framework, to simultaneously and iteratively segment portal images and register them to three-dimensional (3-D) computed tomography (CT) image data. The registration framework has two steps, the max step and the min step, and evaluates appropriate entropies to estimate segmentations of the portal images and to find the transformation parameters. In the initial version of the algorithm (Bansal et al. 1999), we assumed image pixels to be independently distributed, an assumption not true in general. Thus, to better segment the portal images and to improve the accuracy of the estimated registration parameters, in this initial formulation of the problem, the correlation among pixel intensities is modeled using a one-dimensional Markov random process. Line processes are incorporated into the model to improve the estimation of segmentation of the portal images. In the max step, the principle of maximum entropy is invoked to estimate the probability distribution on the segmentations. The estimated distribution is then incorporated into the min step to estimate the registration parameters. Performance of the proposed framework is evaluated and compared to that of a mutual information-based registration algorithm using both simulated and real patient data. In the proposed registration framework, registration of the 3-D CT image and the portal images is guided by an estimated segmentation of the pelvic bone. However, as the prostate can move with respect to the pelvic structure, further localization of the prostate using ultrasound image data is required, an issue to be further explored in future.