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Increases in the number of infections with fluoroquinolone-resistant Neisseria gonorrhoeae in Asia and the United States threaten the efficacy of fluoroquinolones as inexpensive, single-dose, orally administered treatments for gonorrhea. This report describes the findings of a field investigation of an increase in the number of infections with ciprofloxacin-resistant N. gonorrhoeae (CipRGC) in Hawaii in 2001. We conducted a case review of 53 patients with CipRGC, who constituted 20% of the 267 patients with cultures positive for N. gonorrhoeae during this period. Nearly one-half of patients with CipRGC were seen by clinicians in private practice, one-third were seen by clinicians at a sexually transmitted diseases (STD) clinic, and only 2% were seen by clinicians in the military. Among the 117 patients with culture-confirmed gonorrhea who attended the public STD clinic, we found a prevalence of infection with CipRGC of 17%. The demographic and clinical characteristics of patients with CipRGC were similar to those of patients with gonorrhea that was not resistant to ciprofloxacin, suggesting that fluoroquinolone-resistant gonorrhea has become endemic in Hawaii.