Recently evidence has been obtained that a minute amount of cytidine 5'-monophospho-N-acetyl neuraminic acid (CMP-NANA) or a closely related compound is the low Mr factor in human red blood cells which induces Neisseria gonorrhoeae (BS4(agar] to resistance to killing by fresh human serum. Induction of gonococci to resistance by both CMP-NANA and semi-purified low Mr factor from red blood cells was accompanied by a 35-55% reduction of silver staining of lipopolysaccharide separated in SDS-PAGE gels of proteinase K digests. These alterations in lipopolysaccharide are probably responsible for conferring serum resistance. However, lipopolysaccharide-containing digests from resistant as well as from susceptible gonococci neutralised serum bactericidal activity. These observations may have wider implications since CMP-NANA is a sialylating agent wide-spread in mammalian tissues and LPS is ubiquitous amongst Gram-negative pathogens.