A randomized trial was conducted to compare cefixime (400 mg or 800 mg single oral dose) with ceftriaxone (250 mg single intramuscular dose) in terms of efficacy and safety for the treatment of uncomplicated Neisseria gonorrhoeae urethritis or cervicitis. Of 75 men and 150 women screened, 187 had positive culture results for N. gonorrhoeae. The course of treatment was evaluable in 155 cases (59 men, 96 women). Bacteriologic eradication was evident in 97% (105 out of 108) of the patients treated with cefixime and in 100% (47 out of 47) of the patients treated with ceftriaxone. N. gonorrhoeae was eliminated at 98% (143 out of 146) and 100% (72 out of 72) of the infection sites in the respective treatment groups. Of the 187 isolates, 8 were penicillinase-producing (PPNG) and 20 had high-level tetracycline resistance (TRNG). The cefixime and ceftriaxone MIC90 for all 187 study isolates was 0.008 micrograms/ml. The adverse clinical experiences reported by the patients treated with cefixime (10%) were self-limiting; no adverse experiences occurred in the patients treated with ceftriaxone. Cefixime was as well tolerated and efficacious as ceftriaxone in the treatment of the patients with uncomplicated N. gonorrhoeae urethritis or cervicitis reported here.