Because of the widespread existence of Neisseria gonorrhoeae resistant to penicillin or tetracycline, ceftriaxone is now recommended for the treatment of gonorrhea. There is, however, a need for effective antibiotics that can be administered orally as an alternative to ceftriaxone, which requires intramuscular administration. Cefixime is an orally absorbed cephalosporin that is active against resistant gonococci and has pharmacokinetic activity suitable for single-dose administration. In a randomized, unblinded multicenter study of 209 men and 124 women with uncomplicated gonorrhea, we compared three single-dose treatment regimens: 400 mg or 800 mg of cefixime, administered orally, and 250 mg of ceftriaxone administered intramuscularly. The overall cure rates were 96 percent for the 400-mg dose of cefixime (89 of 93 patients) (95 percent confidence interval, 93.5 to 97.8 percent); 98 percent for the 800-mg dose of cefixime (86 of 88 patients) (95 percent confidence interval, 94.6 to 100 percent); and 98 percent for ceftriaxone (92 of 94 patients) (95 percent confidence interval, 94.9 to 100 percent). The cure rates were similar in men and women, and pharyngeal infection was eradicated in 20 of 22 patients (91 percent). Thirty-nine percent of 303 pretreatment gonococcal isolates had one or more types of antimicrobial resistance; the efficacy of all three regimens was independent of the resistance pattern. Chlamydia trachomatis infection persisted in at least half the patients infected in each treatment group. All three regimens were well tolerated. In the treatment of uncomplicated gonorrhea, a single dose of cefixime (400 or 800 mg) given orally appears to be as effective as the currently recommended regimen of ceftriaxone (250 mg given intramuscularly). (N Engl J Med 1991;325:1337–41.) © 1991, Massachusetts Medical Society. All rights reserved.