Bone scintigraphy is the most frequent examination among various diagnostic nuclear medicine procedures. It is a well-established imaging modality for the diagnosis of osseous metastasis and for monitoring osseous tumor response to chemotherapy and radiation therapy. Although the sensitivity of bone scan examinations for detection of bone abnormalities has been considered to be relatively high, it is time consuming to identify multiple lesions such as bone metastases of prostate and breast cancers. In addition, it is very difficult to detect subtle interval changes between two successive abnormal bone scans, because of variations in patient conditions, the accumulation of radioisotopes during each examination, and the image quality of gamma cameras. Therefore, we developed a new computer-aided diagnostic (CAD) scheme for the detection of interval changes in successive whole-body bone scans by use of a temporal subtraction image which was obtained with a nonlinear image-warping technique. We carried out 58 pairs of successive bone scans in which each scan included both posterior and anterior views. We determined 107 "gold-standard" interval changes among the 58 pairs based on the consensus of three radiologists. Our computerized scheme consisted of seven steps, i.e., initial image density normalization on each image, image matching for the paired images, temporal subtraction by use of the nonlinear image-warping technique, initial detection of interval changes by use of temporal-subtraction images, image feature extraction of candidates of interval changes, rule-based tests by use of 16 image features for removing some false positives, and display of the computer output for identified interval changes. One hundred seven gold standard interval changes included 71 hot lesions (uptake was increased compared with the previous scan, or there was new uptake in the current scan) and 36 cold lesions (uptake was decreased or disappeared) for anterior and posterior views. The overall sensitivity in the detection of interval changes, including both hot and cold lesions evaluated by use of the resubstitution and the leave-one-case-out methods, were 95.3%, with 5.97 false positives per view, and 83.2% with 6.02, respectively. The temporal subtraction image for successive whole-body bone scans has the potential to enhance the interval changes between two images, which also can be quantified. Furthermore, the CAD scheme for the detection of interval changes by use of temporal subtraction images would be useful in assisting radiologists' interpretation on successive bone scan images.