A new method is proposed for calculation of the chemical potential of macromolecules by computer simulation. Simulations are performed in an expanded ensemble whose states are defined by the length of a tagged molecule of variable size. A configurational-bias sampling and a preweighting scheme are introduced to facilitate transitions between such states. The usefulness of the method is illustrated by calculations of the chemical potential of hard chain molecules over a wide range of densities. The method proposed here is shown to offer significant advantages over other available methods for calculation of chemical potentials, particularly for long chain molecules at high densities.