We examined 300 strains of Neisseria gonorrhoeae and 100 strains of Haemophilus ducreyi to determine their in vitro susceptibility to two new cephalosporins, cefetamet (Ro 15-8074) and ceftetrame (Ro 19-5247; T-2588), and a new fluroquinolone, fleroxacin (Ro 23-6240; AM-833). Their activity was compared with that of ceftriaxone, penicillin, spectinomycin, tetracycline, and erythromycin. Cefetamet, ceftetrame, and fleroxacin had excellent in vitro activity against both groups of microorganisms. beta-Lactamase production did not significantly affect the MICs of these agents. The Mtr phenotype of N. gonorrhoeae raised the MICs two- to fourfold, but the MICs remained within the range of achievable levels in serum. These newer compounds have a distinct advantage over existing therapeutic agents in that they can be administered orally. Clinical trials are warranted to assess their usefulness in the therapy of gonorrhea and chancroid.