Cefixime was tested in a multilaboratory study to establish susceptibility testing interpretive criteria and quality control (QC) guidelines for Neisseria gonorrhoeae. Interpretive criteria were established by using triplicate testing of 102 representative gonococcal strains. Only a susceptible category was proposed for cefixime (greater than or equal to 31 mm and less than or equal to 0.25 micrograms/ml) because of very rare, resistant isolates. QC ranges [N. gonorrhoeae American Type Culture Collection (ATCC) 49226] were established using multiple GC agar lots, three disk lots, and a number of test replicates consistent with the National Committee for Clinical Laboratory Standards (NCCLS) M23-T guidelines. Cefixime was stable in GC agar medium for at least 21 days when stored at 2 degrees-5 degrees C. Oral third-generation cephalosporins, such as cefixime, appear to represent potentially useful clinical alternatives to parenteral drugs of the same class for single-dose therapy of gonorrhea.