Neisseria gonorrhoeae infection is limited to the human host. Experimental urethral infection in male volunteers was used to study different aspects of the infection. Urethral installation of a variety of gonococcal variants (10(4)-10(6)) led to infection in 27 subjects, who developed pyuria and shed bacteria in urine before urethritis developed 1-6 days after gonococcal inoculation. The incubation period was affected by the inoculation procedure and size of the inoculum. Subjects were treated with intramuscular ceftriaxone (250 mg) if urethritis developed or at 6 days after inoculation. Urine cultures became negative within several hours of therapy, and symptoms resolved within 1 day of therapy. Infected patients suffered no major complications. Experimental male urethral gonococcal infection provides a unique opportunity to understand the biology and immunology of gonococcal infection and is an efficient method to test gonococcal vaccine candidates.