Friction anisotropy was studied between two Pd(100) single-crystal surfaces sliding in an ultrahigh vacuum environment. Friction measurements were made using Pd(100)/Pd(100) interfaces modified by adsorption of octane at coverages ranging from 4 to 40 molecular monolayers (ML). The relative crystallographic orientation of the two Pd(100) surfaces was systematically varied and friction measurements were made at each orientation as a function of octane coverage. These measurements have revealed that friction is anisotropic with respect to Pd(100) lattice orientation. When the surfaces were aligned, forming a commensurate interface, and sheared along the <110> direction with 4 ML of octane at the interface, the static friction coefficient was mu(s) > 8.0 +/- 2.0. A minimum in the static friction coefficient was obtained when the two Pd(100) surfaces with 4 ML of octane at the interface were misoriented by theta = 45degrees. Under these conditions, the static friction coefficient for sliding along the <110> direction of the stationary surface was mu(s) = 4.0 +/- 2.0. Higher coverages of octane decreased the friction, but friction anisotropy persisted for coverages of octane up to 20 ML at the interface. Wear scars were observed on both surfaces indicating that plastic deformation occurred during sliding. The observation of friction anisotropy in the presence of disordered overlayers of octane and during shearing of surfaces that deform plastically suggests that friction anisotropy originates with the properties of the bulk crystal lattices rather than surface lattice commensurability. These results corroborate the findings of a previous study of friction anisotropy between Ni(100) surfaces.