Antibacterial agents are often used in malarial endemic areas for antimalarial prophylaxis (such as doxycycline and clidamycin). Gonococcal infections may coexist in the same geographic area, thus becoming suppressed by compounds directed toward malarial parasites. We tested 11 drugs with activity for Plasmodium species against 105 Neisseria gonorrhoeaestrains. Traditional or investigational antimalarials such as arteflene (Ro 42-1611), chloroquine, primaquine, pyrimethamine, quinacrine, and quinine were observed to be inactive. Fansidar (sulfadoxine-pyrimethamine) and mefloquine possess marginal action in a minority of gonococcus strains (<10%). Doxycycline [minimum inhibitory concentration inhibiting 90% of tested strains (MIC 9 0 ) 2 μg/ml] and azithromycin (MIC 9 0 , 0.5 μg/ml) among the antibacterials were very active, indicating a dual role as antimalarial and antigonococcal agents. Thus, the gonorrhea and sexually transmitted disease epidemiologic data from geographic regions where doxycycline or newer macrolides may be used for malarial prophylaxis or therapy could be significantly altered.