BACKGROUND AND OBJECTIVES: The spread of sexually transmitted diseases (STDs), including gonorrhea, is affected by the duration of infection. Oral antibiotic therapy for gonococcal infection has been shown to be as effective as conventional intramuscular injection with ceftriaxone. Rapid cure would be expected to limit further spread of gonorrhea. However, the speed with which Neisseria gonorrhoeae is eliminated from the urogenital tract has not been evaluated. GOAL OF THIS STUDY: To determine the time required for elimination of Neisseria gonorrhoeae for the urine, mucosa, and semen in male subjects after treatment with ceftriaxone (250 mg intramuscularly), ciprofloxacin (500 mg by mouth, single dose) or cefixime (400 mg by mouth, single dose.) RESULTS: In 14 subjects, gonococci were eliminated from the urine within 4 hours of therapy and the mucosa within 24 hours after therapy. In 9 additional subjects, gonococci were eliminated from the semen by 24 hours after therapy. CONCLUSIONS: These results support the efficacy of single-dose oral therapy for gonorrhea and suggest that earlier follow-up for proof of cure in clinical trials of new antibiotics for gonorrhea may be acceptable. Rapid elimination of gonorrhea reduces the risk for continued transmission of the organism.