SUMMARY When Gram-negative cell walls were damaged by lysozyme and ethylene- diaminetetra-acetic acid (EDTA) in tris buffer, tris played an active role through its action as an organic cation. Other organic cations such as aliphatic amines and quaternary ammonium compounds were more effective than tris in modifying the cell wall and making it permeable to other solutes. The most effective organic cations had one C,, to CI6 alkyl chain. At ~HIo, EDTA roo pg./ml and N,N-dimethyldodecylamine (DDA) 2.5 ,ug./ml. modified the cell wall of Escherichia coli so as to permit a more than 99.99 % kill by 20,ug.fml. of a zwitterionic surface active agent, a-hydroxy-3- (dimethylhexadecylammonio) propane- I -sulphonate (HAPS), in 10 min. at 37'. At these concentrations, the individual compounds were bactericidally ineffective. Four other Gram-negative species were shown to be similarly susceptible to killing by this system. Together, EDTA and DDA appeared to remove surface components of the Gram-negative cell wall. Alone, DDA and other organic cations removed somatic antigens from the cell wall.