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Microstructural cyclic deformation mechanisms and their relation to small fatigue crack initiation and early propagation behavior were experimentally investigated in a rare earth-containing magnesium alloy (Mg-Gd-Y-Zr). The results indicate that basal slip is the dominant deformation mechanism, especially in coarse grains, and eventually leads to fatigue crack initiation. Early crack propagation behavior was strongly influenced by local microstructural heterogeneities in grain size and orientation. Three kinds of microstructures—favorably-oriented coarse grains, fine grain clusters and unfavorably-oriented coarse grains—are discussed in terms of their deformation mechanisms and resistance to crack propagation. These microstructural effects caused highly variable crack propagation rates within the first ∼200 μm of cracks.