The ability of human monocytes to phagocytize and kill nonpiliated opaque (T3) and transparent (T4) gonococci was investigated in a tumbling tube suspension assay. A serum-sensitive strain, F62, and a serum-resistant strain, FA19, were studied. CFU remaining after incubation with monocytes were used to assess the extent of killing. The data show that 50% of T3 and T4 gonococci of both strains were killed by monocytes over a 2-h period. Serum was necessary for the killing of transparent gonococci of both strains as well as for FA19 T3. Concentrations of serum ranging from 0.5 to 10% were equally effective, and heat-labile components were required. Killing of F62 T3, however, occurred in the absence of serum. An increased ratio of bacteria to monocytes decreased the rate of killing. A 30-min preopsonization of gonococci in 10% serum resulted in an enhanced rate of killing. Monocytes were able to kill plate-grown, but not log-phase, organisms. Disruption of the monocytes by sonication to release internalized bacteria did not increase the number of viable organisms. The addition of 10 micrograms of cytochalasin B per ml completely inhibited the reduction in colony numbers over time. These data indicate that freshly isolated human monocytes are capable of phagocytizing and killing nonpiliated gonococci.