The inversion of four 1,4-benzodiazepines was investigated with the ab initio "replica path method" with density functional theory at the B3LYP/6-31G* level. The reaction path constructed with this method for the inversion provides an approximate transition state (TS) geometry, which, upon further TS optimization, leads to the TS geometry characterized by a single vibrational frequency. 1,4-Benzodiazepines lacking a 5-phenyl ring have a single reaction path for the inversion with C-s symmetry at the TS. In contrast, the inversion of benzodiazepines with a 5-phenyl ring, such as the peripheral benzodiazepine receptor ligand 4'-chlorodiazepam (Ro5-4864) and its N-1-desmethyl analog (Ro5-2752), can proceed through multiple reaction paths having a TS with or without CS symmetry. Notably, the replica path method found a path connecting two asymmetric TSs of 4'-chlorodiazepam via a symmetrical TS, suggesting that these inversion paths can be readily crossed from one to another. The stabilization energies gained by 4'-chlorodiazepam and its N-1-desmethyl analog from the breaking of C-s symmetry at the TS were calculated to be 0.10 and 0.07 kcal/mol, respectively. The origin of the broken symmetry of C-s was traced to the coupling of the puckering of the diazepine ring with the rotation of the chlorophenyl ring. These results show the advantages of the replica path method for locating the TSs as well as for constructing the reaction paths for the inversion of 1,4-benzodiazepines.