For earthquake excitation, base isolators have been successfully used in building structures on firm ground. However, the use of these devices in buildings on soft soil for SF6 gas-insulated substations introduces the following concerns: a) the frequency and damping characteristics of the fixed-base structure may change significantly by the combined effects of soil-structure interaction (SSI) and the base isolation device; and b) very large displacements may result because of the translation and rocking of the foundation. In this paper, the effects of SSI on the seismic response of a base-isolated MDOF system are investigated. Both kinematic and inertial effects are considered. The effective input motions (translation and rocking) for an embedded foundation are computed with the averaging Iguchi's method. The soil is replaced by frequency-dependent elastic springs and viscous dampers computed with a finite layer method. The SSI analysis is performed in the frequency domain with the complex frequency method. Numerical results, including floor response spectra of acceleration and displacement, are computed for SSI conditions prevailing in Mexico City, where SF6 gas-insulated substations are being projected. The base isolation device must be capable of accommodating displacements associated with different performance levels.