The genetic mutations within the quinolone resistance-determining regions (QRDRs) of gyrA and parC of 234 Neisseria gonorrhoeae strains isolated in the Far East and the United States, which exhibited either clinically significant ciprofloxacin resistance (CipR) or intermediate ciprofloxacin resistance (CipI) were characterized. A number of GyrA/ParC amino acid alteration patterns were identified, the most prevalent alteration pattern among CipR isolates being GyrA-91,95/ParC-Asp-86- > Asn (91,95/Asp-86- > Asn). Isolates containing 91,95/Asp-86- > Asn belonged to a number of A/S classes, penicillin/tetracycline resistance phenotypes, and plasmid profiles. These results strongly suggest that the continuing emergence of ciprofloxacin-resistant gonococci is not due to the spread of a single or a few strains but to numerous factors such as 'spread of existing strains, importation of new strains and, possibly, de novo development of ciprofloxacin resistance in previously susceptible strains.