The response of the screw dislocation core in a body-centred cubic model lattice to a general applied stress tensor is examined by means of computer simulation. The Peierls stress is found to have the symmetry required by Neumann’s principle but is found also to have a very strong dependence on shear components of the applied stress which should not interact with the screw dislocation. Rather than having the constant value suggested by the Schmid law of critical resolved shear stress, the Peierls stress can vary from zero to the theoretical shear strength of the lattice, depending upon the exact nature of the critical applied stress components. Calculations with different interatomic binding potentials show that the Peierls stress variation, while different in detail, remains broadly the same, suggesting an origin in the dislocation core geometry rather than the specific characteristics of the force laws. Specialization to the case of uniaxial applied stress shows that the similar Peierls stress variation can nevertheless lead to quite different orientation dependences of the flow stress in different materials. Applications to the problem of brittle fracture and possible sources of the Peierls stress variation are discussed briefly.