Ceftibuten, a new oral third generation cephalosporin, was found to be the most active beta-lactam drug tested against members of the Enterobacteriaceae, inhibiting most strains at less than 4 micrograms/ml. All isolates of Branhamella catarrhalis, Haemophilus influenzae, and Neisseria spp. were highly susceptible to ceftibuten. Penicillin-sensitive pneumococci and pathogenic beta-hemolitic streptococci were also killed by ceftibuten. The antibacterial activity of this new drug, which results in rapid lysis of susceptible cells, was not significantly affected by serum, pH, inoculum size, media composition and growth conditions. Ceftibuten is characterized by a remarkable resistance to inactivation by most beta-lactamases synthetized by common gram-positive and gram-negative pathogens. The potent in vitro activity of ceftibuten in conjunction with its favorable pharmacokinetic profile render this new molecule an attractive candidate for the treatment of respiratory and urinary tract infections sustained by susceptible pathogens.