OBJECTIVE To review the antimicrobial activity, pharmacokinetics, clinical efficacy, and tolerability of ceftibuten, a new expanded-spectrum oral cephalosporin. METHODS Literature was identified by a MEDLINE search (January 1983-June 1996) of the medical literature, review of English-language literature and bibliographies of these articles, and data on file. METHODS Clinical efficacy data were selected from all published and unpublished trials and abstracts that mentioned ceftibuten. Additional information concerning in vitro susceptibility, safety, chemistry, and pharmacokinetic profile of ceftibuten also was reviewed. RESULTS Ceftibuten, an oral expanded-spectrum cephalosporin, has a broad spectrum of activity against many gram-negative and selected gram-positive organisms, including Streptococcus pneumoniae, Streptococcus pyogenes, Moraxella catarrhalis, and Haemophilus influenzae. Ceftibuten is stable to hydrolysis by many common beta-lactamases. Ceftibuten is rapidly and almost completely absorbed from the gastrointestinal tract and is primarily eliminated renally as unchanged drug. The elimination half-life of ceftibuten is slightly longer than 2 hours. Efficacy has been demonstrated in a number of clinical trials in adults and children with upper and lower respiratory tract infections (e.g., acute otitis media, pharyngitis, sinusitis, bronchitis) and urinary tract infections. The adverse effect profile is equal to that of comparator agents. CONCLUSIONS Ceftibuten is an alternative to other antimicrobial agents with convenient once-daily dosing in the treatment of upper and lower respiratory tract infections. Similar to other oral expanded-spectrum cephalosporins, ceftibuten has antimicrobial activity against common pathogens of the respiratory tract and is stable in the presence of many beta-lactamases. The clinical choice of an oral expanded-spectrum cephalosporin will be based on patient acceptance, frequency of administration, and cost.