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In this paper, the fatigue cracking possibility in different kinds of copper bicrystals with large-angle grain boundaries (GBs) and copper multicrystals containing some low-angle GBs are compared. The results showed that the fatigue cracks, in the copper bicrystals, always nucleated firstly along GBs no matter whether the GBs are perpendicular or parallel to the stress axis. Whereas, for the copper multicrystals containing low-angle GBs, the persistent slip bands (PSBs) are always the preferential sites to initiate fatigue cracks no matter whether low-angle GBs are perpendicular or parallel to the stress axis. Additionally, the fatigue lives of the GBs, and the [(1) over bar 23] and [(3) over bar 35] grains in the [(1) over bar 23] perpendicular to [(3) over bar 35] and [(5) over bar 913] perpendicular to [(5) over bar 79] bicrystals were measured at different cyclic stresses and strain amplitudes. The results show that intergranular fracture always occurred prior to transgranular Fracture in those bicrystals. The fatigue lives increased in the order of the GB, the [(1) over bar 23] and the [(3) over bar 35] grains in the [(1) over bar 23] perpendicular to [(3) over bar 35] bicrystal under cyclic tension-tension loading. On the other hand, the fatigue life of the GB in the [(5) over bar 913] perpendicular to [(5) over bar 79] bicrystal is about two to three times higher than that in the [(1) over bar 23] perpendicular to [(3) over bar 35] bicrystal. Based on these experimental results from the copper bicrystals and multicrystals, it is indicated that the possibility of fatigue cracking increased in the order of low-angle GBs, PSBs and large-angle GBs. It is suggested that both the PSB-GB mechanism and the step mechanism required for GB fatigue cracking were questionable, and the interaction modes of PSBs with GBs may be more important for intergranular fatigue cracking.