The alternative pathway of complement activation provides the host with a humoral component of the natural defense mechanisms against infectious agents. The six plasma proteins involved in recognition and activation perform a continuous surveillance function that does not require specific antibody to recognize potential pathogens. Discrimination between host and foreign particles occurs because activation of the system is under strict control by regulatory plasma and membrane proteins of the host. Full activation only occurs when the function of these regulators is dampened on the surface of foreign particles. Organisms sensitive to attack by the alternative pathway include bacteria, fungi, certain viruses, virus-infected cells, some tumor cell lines, and human erythrocytes lacking the decay accelerating factor (DAF) in their membrane. Activation of the pathway on these particles results in the deposition of large numbers of C3b molecules and assembly of the cytolytic membrane attack complex. These events trigger, through a variety of mediators, several cellular responses including leukocyte chemotaxis, release of vasoactive amines, hydrolytic enzymes and of arachidonic acid metabolites, adhesion, and phagocytosis.