Context.-Reliable quantification of alpha -fetoprotein (AFP) is critical for clinical diagnosis. Accuracy in AFP analysis relies on traceability to reference materials with confirmed commutability. Objective.-To assess the commutability of the reference materials for AFP. We screened for appropriate reference materials for the calibration of clinical AFP analysis and for application in an external quality assessment scheme. The feasibility of using water to dilute a reference material from the World Health Organization was also evaluated. Design.-Patient serum samples with various levels of AFP were randomly interspersed among AFP reference materials from the World Health Organization, the Beijing Center for Clinical Laboratories, and Beijing Controls and Standards Biotechnology and quality controls from BioRad. The samples were analyzed on 5 different platforms to assess the comparability of the results and commutability of the reference materials. Results.-Significant variations in AFP measurement were observed among the 5 instrument platforms. The Beijing Center for Clinical Laboratories and Beijing Controls and Standards Biotechnology reference materials were commutable across all the instrument platforms. The World Health Organization AFP 72/225 reference material diluted with distilled water was also commutable at high concentrations. The Bio-Rad quality control materials for AFP were commutable among 4 out of 5 instrument platforms. Conclusions.-Our results suggested that the Beijing Center for Clinical Laboratories and Beijing Controls and Standards Biotechnology materials were commutable across all 5 instrument platforms, whereas the Bio-Rad quality controls were limited by the concentration of AFP and the instrument platforms used. Caution needs to be taken in using water to dilute the World Health Organization 72/225 reference material because its commutability is limited to high concentrations.