In 1999, 360,076 cases of gonorrhea were reported in the United States (1). Gonorrhea is a major cause of pelvic inflammatory disease, often leading to ectopic pregnancy and infertility, and it can facilitate human immunodeficiency virus (HIV) transmission (2). During the 1980s, resistance to penicillin and tetracycline among gonococcal isolates became widespread; as a result, CDC recommended that other antimicrobial agents be used to treat gonorrhea. This report summarizes investigations of an increase in fluoroquinolone-resistant Neisseria gonorrhoeae in Hawaii and of a cluster of N. gonorrhoeae infections with decreased susceptibility to azithromycin in Missouri.