Lipopolysaccharides interact with complement only when they are present in a state of high aggregation with a high apparent molecular weight. Lipopolysaccharides in uniform salt forms prepared by electrodialysis and neutralization with different bases exhibited distinct differences in their anticomplementary activity which correlated with differences in their sedimentation coefficients. Conversion of smooth (S) form lipopolysaccharides into the low-molecular-weight triethylamine form completely abolished their anti-complementary activity while conversion into the high-molecular-weight sodium form increased their activity. In contrast, a similar treatment of highly defective Re and Rd rough (R) form lipopolysaccharides had no effect on their ability to interact with complement. Both the triethylamine and sodium forms were strongly anti-complementary despite large differences in their molecular weight. This was found to be due to the property of R lipopolysaccharides to reaggregate into a large-molecular-weight form through absorption of Mg2+ and Ca2+ present in the guinea pig serum used as complement source. Defective lipopolysaccharides derived from the Ra and Rb classes showed only negligible anti-complementary activity which did not increase by conversion into salt forms with high molecular weight.