Salmonella typhimurium and Escherichia coli K12 mutants of R chemotype, with varying contents of major proteins, were studied with respect to serum-mediated killing. The mutants demonstrated a different susceptibility to serum lytic action. These results were related to phospholipid and fatty acid content, as well as different physico-chemical surface properties, such as outer membrane fluidity. Tests were carried out on all parameters considered in the literature to demonstrate the resistance to complement. Our results showed that in sensitive strains such as Salmonella strains SH6261, SH6378, SH5551, SH6017 and E. coli PC0479 tests taken alone were not sufficient to explain the resistance to complement. Therefore, complement susceptibility is probably determined by many factors influencing the microheterogeneity of the membrane system.