Method and system for the detection of interval change in medical images. Three dimensional images, such as previous and current section images in CT scans, are obtained. An anatomic feature, such as the lungs, is used to select sections containing lung by a gray-level thresholding technique. The section correspondence between the current and previous scans is determined automatically. The initial registration of the corresponding sections in the two scans is achieved by a rotation correction and a cross-correlation technique. A more accurate registration between the corresponding current and previous section images is achieved by local matching. A nonlinear warping process which is also based on the cross-correlation technique is applied to the previous image to yield a warped image after the matching. The final subtracted section images were derived by subtracting of the previous section images from the corresponding current section images. Interval changes such as a change in tumor size and a newly developed pleural effusion are enhanced significantly.