Resistance of Neisseria gonorrhoeae to antimicrobial agents continues to spread and intensify. Choosing an antimicrobial regimen requires knowledge of the comparative efficacy of candidate regimens, as delineated in properly conducted clinical trials; their activity against N. gonorrhoeae in vitro; and their pharmacokinetics and toxicity. We tabulated the results of trials of single-dose antimicrobial therapy for uncomplicated gonococcal infection published after 1980. Thirty regimens comprising 21 antimicrobial drugs have been shown to be highly effective for rectal and urogenital infections; the agents involved are cefixime, cefodizime, cefotaxime, cefoxitin, ceftizoxime, ceftriaxone, cefuroxime, cefuroxime axetil, ciprofloxacin, fleroxacin, norfloxacin, ofloxacin, pefloxacin, temafloxacin, azithromycin, aztreonam, netilmicin, rifampin plus erythromycin stearate, sisomicin, and spectinomycin. Few regimens have been shown to be highly effective against pharyngeal infections. Among those antimicrobial agents available for the treatment of uncomplicated gonococcal infections in the United States, ceftriaxone (125 mg), cefixime (400 mg), ciprofloxacin (500 mg), and ofloxacin (400 mg) appear to offer the best balance of proven efficacy and safety.