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The objective of this study was to ascertain the antimicrobial susceptibility of Neisseria gonorrhoeae isolates from 6 South American and 13 Caribbean countries participating in the Gonococcal Antimicrobial Surveillance Program (GASP) from 1990 to 1999.A GASP network of laboratories was launched in the Americas and the Caribbean during the 1990s. Standardized methods and interpretative criteria were established for the isolation of N. gonorrhoeae, strain identification, and determination, and quality control of antimicrobial susceptibility.Two countries (Argentina and Uruguay) maintained continuous surveillance during the study period. Some countries gathered data periodically and several others were unable to initiate antimicrobial surveillance as a result of lack of resources. The percentage of penicillin-resistant N. gonorrhoeae isolated in the region over the decade varied considerably (1.0–11.9% carried chromosomal resistance and 17.9–38.8% produced β-lactamase) with an overall trend to declining numbers of penicillin-resistant isolates. For tetracycline, 7.4% to 36.3% carried chromosomal resistance, whereas 12.0% to 27.4% carried plasmid-mediated resistance. There were no reports of ciprofloxacin-resistant isolates, although N. gonorrhoeae with decreased susceptibility to ciprofloxacin and azithromycin as well as spectinomycin-resistant isolates were identified in some countries.