A bisection sampling method was implemented in path integral simulations of chemical reactions in solution in the framework of the quantized classical path approach. In the present study, we employ a combined quantum mechanical and molecular mechanical (QM/MM) potential to describe the potential energy surface and the path integral method to incorporate nuclear quantum effects. We examine the convergence of the bisection method for two proton-transfer reactions in aqueous solution at room temperature. The first reaction involves the symmetrical proton transfer between an ammonium ion and an ammonia molecule. The second reaction is the ionization of nitroethane by an acetate ion. To account for nuclear quantum mechanical corrections, it is sufficient to quantize the transferring light atom in the ammonium ion-ammonia reaction, while it is necessary to also quantize the donor and acceptor atoms in the nitroethane-acetate ion reaction. Kinetic isotope effects have been computed for isotopic substitution of the transferring proton by a deuteron in the nitroethane-acetate reaction. In all computations, it is important to employ a sufficient number of polymer beads along with a large number of configurations to achieve convergence in these simulations. © 2006 American Chemical Society.