The chemical structures and reactions of penicillins and cephalosporins are reviewed in relation to their effects upon pharmacodynamic properties. The reactive betalactam ring is common to all penicillins and cephalosporin C analogues. This ring opens during acylation of the bacterial wall-building enzymes, but previous opening of the ring by acid or beta-lactamases destroys antibiotic activity.Semisynthetic substitutions may protect the ring by steric hindrance; this may actually inactivate certain penicillinases, so that resistant penicillins may potentiate penicillin G in some circumstances. However, the protective substitutions reduce the intrinsic activity of the synthetic penicillins themselves. Other properties which are affected include absorption, protein-binding, excretion, and possible allergenicity of the drugs. Effects on antibacterial spectrum may possibly be secondary to alteration of lipid solubility.