The rates of the acid catalysed hydrolysis of penicillins and cephalosporins are linear in H_o and, unlike other amides, show no rate maximum with increasing acidity. Electron-withdrawing substituents at C-6 in penicillins decrease the rate of hydrolysis with a ρ_I of ca.4 and they decrease the rate when attached to the amine leaving group. The acylamido-group at C-6 in penicillins, but not at C-7 in cephalosporins, exhibits neighbouring group participation with a rate enhancement of ca. 10³. The absence of penicillenic acid formation from benzylpenicillin in acidic solution is not due to the ionisation of the carboxy-group. These observations are rationalised by a scheme, involving N-protonation and formation of an acylium ion intermediate. The alkaline hydrolysis of penicillins proceeds 10² faster than a β-lactam after correction for substituent effects. There is no evidence for substantial inhibition of amide resonance in the bicyclic β-lactam antibiotics, little evidence to indicate extra strain in these systems and no evidence that expulsion of the leaving group at C-3 in cephalosporins occurs in the transition state.