In areas such as Los Angeles, California, where penicillin-resistant Neisseria gonorrhoeae accounts for 1% or more of all gonorrhea strains isolated, third-generation cephalosporin agents have replaced penicillin as standard therapy. Ceftriaxone, the agent recommended by CDC guidelines, or ceftizoxime, an alternative agent have excellent activity against all strains of N. gonorrhoeae. One hundred seventy-five male patients with clinically and microbiologically confirmed gonococcal urethritis were treated with single-dose ceftizoxime 250 mg IM (50 patients) or 500 mg IM (125 patients). Cure was demonstrated clinically by repeat cultures of urethral discharge in all patients, including those with infections from penicillinase-producing strains of bacteria. None of the patients experienced complications or allergic reactions to ceftizoxime. Given the lower unit-of-use cost of ceftizoxime, its routine in place of ceftriaxone could result in substantial cost savings in those institutions that treat large numbers of patients with uncomplicated gonococcal urethritis.