The ability of normal rabbit serum to kill Escherichia coli J6-2 was measured. With the concentration of serum adjusted so that approximately 2% of the cells survived after 2 h of incubation, there was no killing of the same strain bearing the F-like plasmid R100. Other F-like plasmids also provided the host strain with resistance to serum bactericidal activity, whereas none of the I-like plasmids used provided the host strain with resistance. When E. coli J6-2 bore both R100 and an I-like plasmid, there was some resistance to serum but less than with R100 alone. The effects of lysozyme on E. coli J6-2, which had been treated with tris(hydroxymethyl)aminomethane and ethylenediaminetetraacetate, were not altered by the presence of R100. The plasmids from 16 clinical E. coli isolates were transferred to J6-2N, a nalidixic acid-resistant mutant of J6-2. Four of the 16 plasmids provided J6-2N with resistance to normal rabbit serum.