This study considers a scheme for sampling phase space in large molecules based on Car-Parrinello ab initio molecular dynamics. The scheme makes use of a combined quantum mechanics and molecular mechanics (QM/MM) method augmented with a multiple-time-step technique. This scheme makes it possible to oversample the computationally less expensive MM region relative to the QM domain. The goal here is to provide better ensemble averaging in the MM region that is usually larger in size and therefore typically has a higher decree of configurational variability. It is shown that the multiple-time-step integrator will generate the same trajectory as a standard molecular dynamics integrator. Moreover, with a gradual rescaling of masses, the energy conservation of a multiple-time-step simulation can be satisfied to the same extent as a standard simulation. Finally, it is demonstrated that the multiple-time-step QM/MM method can accelerate the equilibration and configurational sampling of a molecular dynamics simulation as it is used in thermodynamic integration. The scheme is not intended as a tool for generating trajectories in actual dynamics.