Aqueous procaine penicillin, ampicillin, and amoxicillin have been used successfully in treatment of gonococcal infections for many years. Many of the new beta-lactam antimicrobial agents subsequently have proved effective for treating these infections as well. First-generation cephalosporins are less active (by weight) than second-generation cephalosporins, which, in turn, are less active than third-generation drugs. Single-dose therapy of uncomplicated mucosal gonococcal infections with first-generation cephalosporins has resulted in generally unacceptably low cure rates of less than 90% in most studies, whereas parenterally and orally administered second-generation cephalosporins show good clinical efficacy. Both second- and third-generation cephalosporins are active against beta-lactamase-producing Neisseria gonorrhoeae. The extended-spectrum and ureido-penicillins are active in vitro against non-beta-lactamase-producing N. gonorrhoeae and have parallel activity in vivo. Single doses of aztreonam, the first monobactam studied in humans, have also shown excellent clinical efficacy.