Factors that may determine the variable resistance of urinary strains of Escherichia coli to the bactericidal activity of normal human serum have been analysed. No statistically significant difference was found in the amount of lipopolysaccharide (LPS) that could be extracted from serum-sensitive and serum-resistant strains by either the phenol-water or warm-saline techniques. The ratio of LPS O-side-chain sugars to core sugars was not found to be significantly greater in serum-resistant than in serum-sensitive strains. A sugar resembling D-glycero-D-mannoheptose was found in LPS from some of the strains; in one case the sugar was shown to be associated with the O-side chain moiety. Lipopolysaccharides from all but two of the strains contained the E. coli R1 core structure. No consistent difference was observed between serum-sensitive and serum-resistant strains in either the amount of acidic polysaccharide extracted or its red-cell agglutination-inhibiting activity; nor was a clear relationship found between sensitivity to serum and sensitivity to R-specific bacteriophages. It is concluded that no one mechanism of serum resistance explains the response to serum of the E. coli strains examined in this study.