Human antibody to lipooligosaccharide (LOS) from pooled normal human serum (NHS) and human immunne serum globulin (HISG) was isolated by affinity chromatography from a Sepharose column to which Escherichia coli strain J-5 LOS had been conjugated. Fractionated antibody was tested for bactericidal activity against serum-resistant Neisseria gonorrhoeae strains JW31, WR220, or 838 or serum-sensitive strains JW31R or 1074. By enzyme-linked immunosorbent assay the eluate of antibody to LOS contained IgM, IgA, and IgG antibodies to both JW31 and JW31R LOS. The IgM fraction from NHS was bactericidal at 30 min for strains JW31R and 1074 but failed to kill strains JW31 and 838. An IgG fraction from HISG was bactericidal for strains JW31 and WR220 yet failed to kill strain JW31R. The IgA fraction from NHS did not kill either strain JW31 or JW31R. Blocking experiments indicated that IgA or IgG failed to prevent IgM-mediated killing of strain JW31R, whereas IgA blocked the IgG-mediated killing of strain JW31.