The alternative complement pathway can be activated in the absence of specific antibody by the surface of certain cells and particles that provide a microenvironment in which the affinity of the regulatory protein H for surface-bound Cab is low. There is now abundant evidence that antibody can enhance activation. Evidence for a role of antibody independent of its classical-pathway function has accrued from experiments with purified proteins of the alternative pathway, sera genetically deficient in C4 and C2, and chelating agents specific for calcium so as to prevent activation of C1. Three models have been employed to demonstrate a function of antibody in the alternative pathway: complexes of antibody with soluble antigen; antibody directed against naturally occurring particulate activators, including zymosan, rabbit and mouse erythrocytes, the pneumococcus, and several types of virus-infected, mammalian cells [17]; and antibody directed against certain nonactivating particles, such as the streptococcus [17]. Because antibody may exert its effect in these systems by different mechanisms, each system will be discussed separately.