The neutron production in thick targets irradiated with 1 GeV protons was studied experimentally, and results are well understood with model calculations, including MCNPX 2.7a. However, one observes very large neutron production rates in the interaction of 44 GeV 12C onto thick Cu-, Pb-, and U-targets beyond calculated rates. The experimental spallation product yield curve in a 20 cm thick Cu target irradiated with 72 GeV 40Ar also cannot be reproduced by several model codes, including MCNPX 2.7a. This may be due to secondary fragments produced in high energy ( GeV) heavy-ion interactions which destroy target nuclei more effectively than primary ions. These observed experimental facts constitute “unresolved problems” from a fundamental point of view. It may have an impact on radiation protection issues for future heavy-ion accelerators.