OBJECTIVE Hypermobility of the craniocervical junction (CCJ) in patients with Down syndrome (DS) is common. Whereas atlantoaxial (C1-2) hypermobility is well characterized, occipitoatlantal (Oc-C1) laxity is recognized but poorly defined. A clear understanding of the risks associated with DS-related hypermobility is lacking. Research efforts to address the topic of axial cervical spine instability in the patient with DS require a reliable and reproducible means of assessing CCJ mobility. The authors conducted a pilot study comparing two methods of quantifying motion of the CCJ on dynamic (flexion/extension) plain radiographs: The delta-condyle-Axial interval (×CAI) and the delta-basion-Axial interval (×BAI) methods. METHODS Dynamic radiographs from a cohort of 10 patients with DS were evaluated according to prescribed standards. Independent movement of Oc-C1, C1-2, and Oc-C2 was calculated. Interrater and intrarater reliability for CCJ mobility was then calculated for both techniques. RESULTS Measurement using the ×CAI technique had excellent fidelity with intraclass correlation coefficients (ICCs) of 0.77, 0.71, and 0.80 for Oc-C1, C1-2, and Oc-C2, respectively. The ×BAI technique had lower fidelity, yielding respective ICCs of 0.61, 0.65, and 0.50. CONCLUSIONS This pilot study suggests that ×CAI is a superior measurement technique compared to ×BAI and may provide reliable assessment of the mobility of the CCJ on dynamic radiographs in the pediatric patient with DS. The use of reliable and reproducible measurement techniques strengthens the validity of research derived from pooled database efforts.