The effect of Ag interlayers 0, 60, 420, and 900 nm thick on the reaction of Ni with Fe in epitaxial Ni(001)/Ag(001)/Fe(001) trilayers has been studied by XRD, volume magnetocrystalline anisotropy, and magnetization measurements. Minor mixing was observed at the interface between Ag(001)/Ni(001) and Ag(001)/Fe(001) bilayers at temperatures above 900 K. When the epitaxial Ni(001)/Ag(001)/Fe(001) trilayer undergoes thermal annealing, a total atomic exchange between Ni and Ag occurs independently of an Ag interlayer thickness. Solid-state synthesis of alloy phases was found to occur in the sequence Fe/Ni → Ni3Fe NiFe → γpar (Fe3Ni-like phase). Temperatures for the formation of Ni3Fe and NiFe phases slightly increase with increasing interlayer thickness, while the initiation temperature for the γpar phase remains intact. We suggest some scenarios for the observed atomic exchange in the system under consideration. The results are rationalized in terms of long-range chemical interaction between Ni and Fe via an Ag interlayer. This means that Ni reacts with Fe despite the fact that a separation between the above atoms is greater than the length of normal chemical bond by a factor of about 104.