Stress echocardiography is a routinely used clinical procedure to diagnose cardiac dysfunction by comparing wall motion information in prestress and poststress ultrasound images. Incomplete data, complicated imaging protocols and misaligned prestress and poststress views, however, are known limitations of conventional stress echocardiography. We discuss how the first two limitations are overcome via the use of real-time three-dimensional (3-D) ultrasound imaging, an emerging modality, and have called the new procedure "3-D stress echocardiography." We also show that the problem of misaligned views can be solved by registration of prestress and poststress 3-D image sequences. Such images are misaligned because of variations in placing the ultrasound transducer and stress-induced anatomical changes. We have developed a technique to temporally align 3-D images of the two sequences first and then to spatially register them to rectify probe placement error while preserving the stress-induced changes. The 3-D spatial registration is mutual information-based. Image registration used in conjunction with 3-D stress echocardiography can potentially improve the diagnostic accuracy of stress testing.