Inherent serum resistance and the effect of the serum resistance inducing factor cytidine 5'-monophospho-N-acetylneuraminic acid (CMP-NANA) were studied on Neisseria gonorrhoeae with different lipopolysaccharides (LPS). Strain M01 and LPS variants of strain Gc40 (variants D1, D2, D4 and D5) were examined after incubation in the presence or absence of CMP-NANA by bactericidal assays using normal human or immune sera and by SDS-PAGE followed by silver staining or Western blotting. The blots were probed with monoclonal antibody CC1, specific to epitope C of the LPS. Variants D1 and D5 were inherently serum resistant, variants D2 and D4 and strain M01 were susceptible. CMP-NANA induced marked changes in the LPS of all gonococci. However, only some gonococci were converted to serum resistance. Gonococci which were converted to serum resistance had LPS with components of relatively large molecular mass, expressing epitope C. Variants which did not convert to serum resistance had LPS with low molecular mass components only, without epitope C. Conversion to serum resistance increased the size of the large LPS components without affecting the expression of epitope C. The results indicate that conversion to serum resistance by CMP-NANA is not a general occurrence but depends on the quality of the LPS.