The thermochemistry of bicyclic lactams (penams, penems, cephams, cephems), which are key pharmacophores in beta-lactam antibiotics, has been investigated by high-level ab initio methods. Particular attention has been paid to estimating magnitudes of amide resonance (ARE) and ring strain (RSE) in the four-member lactam ring because these quantities are difficult to measure and distinguish experimentally. The ring strain destabilization effect is greater than the stabilization arising from amide resonance. However, in cephemes the amide resonance stabilization slightly exceeds destabilization due to the beta-lactam ring strain.