The progression of osteoarthritis (OA) can be monitored by measuring the minimum joint space width (mJSW) between the edges of the femoral condyle and the tibial plateau on radiographs of the knee. This is generally performed by a trained physician using a graduated magnifying lens and is prone to the subjectivity and variation associated with observer measurement. We have developed software that performs this measurement automatically on digitized radiographs. The test data consisted of 180 digitized radiographs of the knee (90 duplicate acquisitions) from 18 normal (nonarthritic) subjects and 38 images from 10 subjects with OA. These were digitized and manually cropped so that the images were free of nonanatomical structures and the knee was approximately centered. The software first determined the edge of the femoral condyle on 400 microm pixel subsampled images. Contours marking the location of the tibial plateau in the medial compartment were found on 100 microm images using the femoral edge as a reference. The algorithm was trained using an independent but similar data set and using a jackknife approach with the test data. The results were compared to contours drawn by a trained reader and the duplicate acquisitions were used to measure the reproducibility of the mJSW measurement. The reproducibility was 0.16 mm and 0.18 mm for normal and osteoarthritic knees, respectively, representing an improvement of approximately a factor of 2 over manual measurement. The algorithm also showed excellent agreement with the hand-drawn contours and with mJSW determined by the manual method.