A kinetic study on the degradations of cefaclor and cefatrizine was carried out at 35°C as a function of pH and initial drug concentration by the use of high-performance liquid chromatography. At constant pH and temperature, the degradation followed pseudo-first-order kinetics at the initial concentration of 5 mM. The shape of the rate-constant-pH profile of cefaclor resembled those for cefatrizine and other aminocephalosporins. At neutral pH, cefaclor was degraded via intramolecular nucleophilic attack of the α-amino group on the β-lactam moiety. The intramolecular reaction rate was very similar to that in the cases of cefatrizine and cephaloglycine, but was ten times faster than those for cefadroxil, cephalexin, and cephradine under the same conditions. Accelerated degradations of the highly reactive aminocephalosporins, cefaclor and cefatrizine, were observed at higher drug concentrations than 10 mM. By simultaneously assaying the disappearances of the α-amino group and the antibiotic itself, it has been confirmed that both antibiotics undergo self-aminolysis in solution through a nucleophilic attack of the free side-chain amino group in one molecule upon the β-lactam bond of a second molecule, forming a dimer. Since the degradation rates of cefaclor and cefatrizine were found to be larger than those of other amino-β-lactam antibiotics, the second-order degradation rate process should be considered in the analysis of their in situ intestinal absorption rates at high concentrations. The above kinetic data were applied to the intestinal absorption of both antibiotics in rats. The disappearance rate of the antibiotics from the intestinal perfusate was successfully interpreted in terms of a combination of Michaelis-Menten absorption, first-order absorption, first-order degradation and second-order dimerization.