Zirconium alloys used as cladding tubes for the fuel of pressurized water reactors can undergo high applied stress during power transients. In these conditions, biaxial loading may lead to plastic deformation of the cladding. A comprehensive understanding of the material mechanical response during loading-path change tests is an important step toward predicting the behavior in these specific conditions. Using a nonstandard mechanical testing machine, we conducted loading-path change tests at 623 K on as-received recrystallized Zircaloy-4 tubes. These tests consisted of an axial tensile loading and unloading followed by an internal pressure (or pure hoop tension) loading and unloading. These tests examined the kinematic and isotropic hardening components of the strain hardening behavior of the thin cladding tubes. The isotropic hardening was attributed to dislocation multiplication and dislocation-dislocation interactions. The kinematic hardening was attributed to the interaction of the grains with each other. A polycrystalline model was also used and improved in order to simulate the tests. A good prediction of the isotropic and kinematic hardening was provided by the modeling.