Thermo-ionic Vacuum Arc evaporation method was selected for the synthesis of Fe/Cu/Ni/Cu multilayer structures on Si (1 0 0) substrates. The aim of the study was the preparation and characterization of structures featuring a giant magnetoresistance effect. This was accomplished by inducing the formation of nanosized ferromagnetic crystallites in multilayer nonmagnetic solutions via atomic inter-diffusion processes by the tuning of deposition parameters. Layer-by-layer and inter-diffused type structures were prepared and comparatively analyzed by scanning electron microscopy, X-ray microanalysis, atomic force microscopy, X-ray diffraction and high-resolution transmission electron microscopy coupled with selected area electron diffraction. We presented the influence of the microstructure on electric and magnetic properties of the submicron-sized multilayers. The dependence of the electric resistance and the magnetoresistance on the composition, structure, morphology and roughness of the layers was established. We obtained an electric resistance value of 1.22 Omega for the layer-by-layer type structure, and 0.46 Omega for the inter-diffusion designed structure. Using the atomic inter-diffusion we succeeded in achieving an improvement of the magnetoresistive effect, from 0.1% to 2.3%. (C) 2015 Elsevier B.V. All rights reserved.