Neisseria gonorrhoeae were exponentially killed for 120 min (i.e., they were prevented from forming colonies on agar) by extracts of human neutrophil granules; however, macromolecular synthesis, indicated by incorporation of radiolabeled precursors in trichloroacetic acid-precipitable material, continued at or above zero time control values for 45 min. Protein, deoxyribonucleic acid, and ribonucleic acid synthesis appeared to decrease simultaneously after 45 min. Little or no lysis of gonococci occurred during the first 60 min of incubation. The ions K+, Na+, Ca2+, Cll-, S042and PO43at concentrations of l100 mM did not affect granule extract bactericidal activity. On the other hand, 20 mM Mg2+ completely inhibited killing when initially present along with granule extract or when added within 2 to 5 min after granule extract was added to a suspension of gonococci. Gonococci treated with granule extract, washed, and then incubated in the absence of extract died as if extract were still present. The ability of subinhibitory concentrations of actinomycin D or erythromycin to inhibit growth and protein and nucleic acid synthesis was synergistically increased in the presence of granule extract. The above information suggests that a bactericidal component(s) of human neutrophil granules sticks to gonococci, altering their outer membrane permeability and their ability to divide. MATERIALS AND METHODS Bacteria. N. gonorrhoeae strain F62 was obtained