A recent study afforded us the opportunity to collect pre- and post-treatment isolates of Neisseria gonorrhoeae from women who supposedly failed to eradicate the organism when tested 8 to 10 days following treatment with a single, directly observed 250-mg dose of ciprofloxacin. In an attempt to differentiate true treatment failure from reinfection, we determined the ciprofloxacin MICs and performed auxotyping, serotyping, and opa typing of the pre- and post-treatment isolates. Paired isolates of N. gonorrhoeae were obtained from seven different women, despite susceptibility of the initial isolates to ciprofloxacin. Six of seven patients were infected with gonococcal isolates that differed significantly from their primary isolate. These most probably represent reinfection with a different strain, which could originate from the same partner infected with multiple strains or reinfected with a new strain or from a different partner. The susceptibility to ciprofloxacin of all isolates makes the possibility of multiple strains in the patient unlikely. The diversity of the isolates within the pairs therefore suggests rapid reinfection within the partnerships.