The factors controlling lysis of gram-negative bacteria by complement are being investigated systematically. The first question was how smooth Salmonella minnesota, which has on its surface lipopolysaccharide with long O polysaccharide side chains, avoids lysis. Rough organisms are serum sensitive. In both smooth and rough organisms, complement components are deposited on the surface and the lytic sequence proceeds to completion. However, with serum-resistant organisms the membrane attack complex (MAC), composed of late-acting complement proteins, does not successfully insert into the outer membrane to cause membrane damage. At the completion of the lytic sequence, the hydrophobic MAC is shed. C3b, which directs late component assembly, is deposited on the longest O polysaccharide side chains on these smooth organisms, where it does not direct successful insertion of the MAC into the outer membrane. Serum-resistant gonococci sequester the MAC on the organism's surface in association with specific outer membrane components, where it does no damage to the outer membrane. Antibody appears to mediate site-directed complement component deposition in a number of systems. Thus, depending on antibody specificity, complement may be deposited on the organism's surface to cause successful complement attack or may block complement attack induced by bactericidal antibody. Monoclonal antibodies of the same isotype directed at different epitopes on the same bacterial surface antigen may either induce lysis or block lytic attack.