Abstract Cyclic deformation and fatigue properties of TiAl polysynthetically twinned (PST) crystals were investigated by focusing on the effect of lamellar structure and plastic anisotropy on the cyclic hardening and fatigue life. Cyclic tension/compression testing at room temperature at total strain-controlled amplitude was carried out on Ti-49.1 at.% Al and Ti-50.8 at.% Al PST crystals containing fine and coarse lamellae, respectively. Strong anisotropic behaviour was observed, depending on the angle (φ) between the loading axis and the lamellar planes. As the strain amplitude was increased, the stress amplitude rose with increasing number of cycles and the cyclic hardening became large at φ = 0, while at φ = 45° specimens exhibited weak cyclic hardening and broke without significant hardening. Although the lamellar spacing in TiAl PST crystals did not lead to much difference in the cyclic hardening rate, refinement of lamellae prolonged the fatigue life in both orientations. The lamellar boundaries act as an effective barrier to the propagation of microcracks crossing the boundaries at φ= 0. The cyclic hardening and fatigue life of specimens with φ = 0 are sensitive to the deformation substructure, particularly with regard to the number of domains in which ½<110]-type ordinary dislocations form a densely tangled and piled-up substructure. The cyclic hardening and fatigue life of crystals with φ= 0 also depends upon the rotation angle (χ) between the loading axis and the ⟨112⟩ direction on (111) lamellar planes in the γ matrix.