The resistance mechanisms associated with changes in the outer membrane permeability and in β -lactamase and penicillin-binding-protein production are reviewed. The prevalence of membrane permeability- and chromosome-mediated β -lactamaserelated resistance in Gram-negative bacteria, and of PBP-related resistance in Gram-positive bacteria, with respect to third-generation cephalosporins, is outlined. The frequency of overall resistance to these compounds in two Parisian hospitals during 1983 did not exceed 2% in Enterobacteriaceae but was close to 15% in Pseudomonas sp.