Lateral flexion-extension radiographs of 72 patients with Down syndrome were used to assess the interobserver reliability and intraobserver reproducibility of the atlanto-dens interval, Wiesel-Rothman measurement, occiput atlas angle, and Power's ratio in flexion and extension. The radiographs were reviewed by three blinded observers on three different occasions with at least a 1-month interval between assessments. The intraclass correlation coefficient was used to measure the reproducibility of the measurements from a given observer and the reliability between different observers. With the exception of observer one, the atlanto-dens interval had a statistically significant intraobserver agreement compared with any of the other measurements (p < 0.05). The atlanto-dens interval and the Wiesel-Rothman measurements tended to have better correlation between observers, although there was only fair agreement. The agreement, however, was statistically significant (p < 0.05) compared with Power's ratio. The degree of intraobserver reproducibility and interobserver reliability may make it difficult to base treatment protocols on these measurements.