The cephalosporins are undergoing molecular manipulations similar to those of the semisynthetic penicillins which were so productive. The cephalosporins are very active against all commonly encountered gram-positive cocci except enterococci and are somewhat more active against gram-negative bacilli than the penicillins, except for carbenicillin which is more active against Enterobacter, indole-positive Proteus, and Pseudomonas aeruginosa than any other antibiotic in these two classes of compounds. β-lactamases specific for the cephalosporins rapidly inactivate the drugs. The cephalosporins may be divided into three general categories on the basis of their clinical pharmacological properties, those with rapid renal clearance (cephalothin), those with significantly slower clearance (cephaloridine and cefazolin) , and those well absorbed after oral administration (cephalexin and cephadrine). Renal excretion of the cephalosporins is by both glomerular filtration and the same tubular transport mechanism responsible for secretion of the penicillins. The prolonged half-life of some of the cephalosporins in plasma is a significant advantage. Indications for use are similar to those for the penicillins, except for infections due to enterococci, Haemophilus influenzae, and bacterial meningitis. Clinically significant cross-reactivity with the penicillins due to hypersensitivity is uncommon, although the types of drug reactions to the cephalosporins are similar to those to the penicillins. Large doses of the cephalosporins may damage the cells of the proximal convoluted renal tubules in experimental animals. The rabbit is quite susceptible, but the rat is relatively resistant. In man this has been observed particularly with cephaloridine. The mechanism for this as well as the influence of drug interactions and other host factors on its occurrence remain unclear.