The influence of substrate morphology is critical to an understanding of hetero-epitaxial growth in metal-metal systems. We have studied vapour deposition of Au on Ru(100) which differs significantly from the extensively studied Au/Ru(001) system. For example, Au deposition at 300 K results in non-pseudomorphic, simultaneous multilayer (SM) growth in contrast to the layer-by-layer pseudomorphic growth characteristic of Au on Ru(001). SM growth is demonstrated by AES, TDS, XPS, ARUPS and LEED; the latter shows development of a series of (1 × n) patterns (n = 3, 4, 5,...) from 0.5 ML Au upwards, indicating formation of close-packed Au chains along the [010] Ru direction. This is consistent with attractive Au-Au interactions, confirmed by a complete lineshape analysis of the Au thermal desorption spectra which shows an 85 kJ/mol increase in the desorption activation energy in the 0–0.3 ML coverage region. At coverages ≳ 15 ML the Au overlayer adopts an fcc Au(111)-like arrangement oriented with the Au[110] axis parallel to Ru[010]. For coverages < 10 ML, LEED, AES and XPS data obtained after annealing to 1075 K indicate that the observed SM growth is not a result of kinetic limitations and that differences in behaviour between this system and Au/Ru(001) can be attributed to the anisotropic nature of the Ru(100) substrate. Thermal desorption spectra show a multilayer desorption peak only after ∼ 2 ML Au deposition, despite the SM growth mode, indicating quasi-melting and spreading of the overlayer at temperatures close to desorption. Au coverages> 8 ML undergo a complete structural rearrangement involving after annealing to ∼ 1050–1100 K. The rearrangement was indicated by development of a new LEED pattern and changes in the He I valence band spectra