Enthalpies for the beta-scission reactions, R'SC center dot(Z)SR -> R'SC(Z)=S + R-center dot (for R, R' = CH3, CH2CH3, CH2CN, C(CH3)(2)CN, CH2COOCH3, CH(CH3)COOCH3, CH2OCOCH3, CH2Ph, C(CH3)(2)Ph, and CH(CH3)Ph and Z = CH3, H, Cl, CN, CF3, NH2, Ph, CH2Ph, OCH3, OCH2CH3, OCH(CH3)(2), OC(CH3)(3), and F) have been calculated using a variety of DFT, MP2, and ONIOM-based methods, as well as G3(MP2)-RAD, with a view to identifying an accurate method that can be practically applied to larger systems. None of the DFT methods examined can reproduce the quantitative, nor qualitative, values of the fragmentation enthalpy; in most cases the relative errors are over 20 U mol(-1) and in some cases as much as 55 U mol(-1). The ROMP2 methods fare much better, but fail when the leaving group radical (R-center dot) is substituted with a group (such as phenyl or CN) that delocalizes the unpaired electron. However, provided the primary substituents on the leaving group radical are included in the core system, an ONIOM-based approach in which the full system is studied via ROMP2 (or SCS- or SOS-MP2) calculations with the 6-311 +G(3df,2p) basis set and the core system is studied at G3(MP2)-RAD can reproduce the corresponding G3(MP2)-RAD values of the full systems within 5 U mol(-1) and is a practical method for use on larger systems.