Normal human serum (NHS) killed Neisseria gonorrhoeae (GC) strain F62 after incubation at 37 degrees C. In contrast, the bactericidal effect of normal guinea pig serum (NGPS) under similar conditions was not obvious. When NHS was mixed with NGPS or heated NGPS and a suspension of strain F62, the bacteria were protected from killing by NHS. When strain F62 was incubated first with NGPS for 30 min at 37 degrees C, washed and then treated with NHS, the strain was significantly protected. Depletion of complement (C) of NGPS by zymosan treatment or by heating at 56 degrees C for 30 min decreased the protective activity of NGPS. These data suggest that protection of GC by NGPS occurred on the surface of GC and C may be involved. However, when strain F62 was incubated first with heated NGPS for 30 min at 37 degrees C, washed and then treated with NHS, the strain was significantly killed. This suggests that protection of GC by heated NGPS did not occur on the surface of GC. In addition to the protective effect of NGPS on the bactericidal activity of NHS for GC, NGPS adsorbed with strain F62 also had the ability to kill the GC.