Of the currently recommended regimens for treatment of uncomplicated gonorrhea, only aqueous procaine penicillin G is effective against infections of all sites. However, this agent is not effective against penicillinase-producing Neisseria gonorrhoeae and suffers from poor patient acceptability owing to the 10-ml volume of injection and to allergic and toxic reactions to procaine. Ceftriaxone is a new, extended-spectrum cephalosporin with a long serum half-life and is many times more active than penicillin G against both beta-lactamase-positive and -negative strains of N. gonorrhoeae. In clinical trials ceftriaxone, in a single intramuscular dose of 125 or 250 mg, has proved as effective as any other regimen in the treatment of uncomplicated gonococcal infections of the pharynx, anorectum, cervix, and urethra. Thus, ceftriaxone (125 mg) should be considered a drug of choice for uncomplicated gonorrhea, particularly where homosexual men are treated and penicillinase-producing N. gonorrhoeae and/or chromosomally mediated resistance is prevalent.