Molecular dynamics simulations of macromolecules require long computation times to generate the trajectories needed for determining their thermodynamic and dynamic properties. The most rapidly varying quantities, such as the bond lengths, limit the integration time step, while the more slowly varying molecular processes are of primary interest. The form of the empirical potential energy function used in simulations of macromolecules makes it possible to exploit the existing separation of time scales by use of the reversible multiple time-step method (Tuckerman, Berne, and Martyna. J. Chem. Phys. 1992, 97, 1990). Implementation of the method in Cartesian coordinates yields an efficient multiple time-step algorithm for molecular dynamics with a velocity Verlet integrator.