The strain and resonance energies in beta-sultam derivatives have been calculated by using a high-level ab initio method (G3/B3LYP) in order to resolve the question of the principal driving force affecting solvolysis of these new antibiotics. We found that only the combined effect of stabilizing (via amide or sulfonamide resonance interactions) and destabilizing (ring strain) influences can account for the observed rates of solvolysis in beta-lactams and beta-sultams.