Background and Objectives: Cefotaxime is a third-genera- tion cephalosporin that has in vitro activity against Neisseria gonorrhoeae, including B-Iactamase-producing strains. A single 1-g intramuscular dose is effective and is recommended by the Centers for Disease Control and Prevention as an alternative treatment for uncomplicated gonorrhea. Goal of this Study: This study was conducted to evaluate the efficacy and safety of a lower 500-mg dose of cefotaxime in the treatment of uncomplicated gonococcal infections. Study Design: In a randomized multicenter study, patients who had uncomplicated gonorrhea were treated with 500 mg of cefotaxime or 250 mg of ceftriaxone. Both antibiotics were given intramuscularly. Efficacy and safety were assessed four to seven days following treatment. Results: Six hundred thirteen patients were enrolled. Bacteriologic eradication rates for anogenital infection were 97.7% of the patients (213/218) in the cefotaxime group and 99.1% of the patients (221/223) in the ceftriaxone group (P = 0.243). Adverse events occurred in 4.2% and 7.5% of patients in the two groups, respectively. Conclusion: Cefotaxime 500 mg appears to be a safe and cost-effective alternative to ceftriaxone 250 mg for the treatment of uncomplicated gonorrhea. © Copyright 1993 American Sexually Transmitted Diseases Association.