The N/Z dependence of projectile fragmentation at relativistic energies has been studied with the ALADIN forward spectrometer at the GSI Schwerionen Synchrotron (SIS). Stable and radioactive Sn and La beams with an incident energy of 600 MeV per nucleon have been used in order to explore a wide range of isotopic compositions. For the interpretation of the data, calculations with the statistical multifragmentation model for a properly chosen ensemble of excited sources were performed. The parameters of the ensemble, representing the variety of excited spectator nuclei expected in a participant-spectator scenario, are determined empirically by searching for an optimum reproduction of the measured fragment-charge distributions and correlations. An overall very good agreement is obtained. The possible modification of the liquid-drop parameters of the fragment description in the hot freeze-out environment is studied, and a significant reduction of the symmetry-term coefficient is found necessary to reproduce the mean neutron-to-proton ratios N/Z and the isoscaling parameters of Z≤10 fragments. The calculations are, furthermore, used to address open questions regarding the modification of the surface-term coefficient at freeze-out, the N/Z dependence of the nuclear caloric curve, and the isotopic evolution of the spectator system between its formation during the initial cascade stage of the reaction and its subsequent breakup. © 2011 American Physical Society.