Antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells describes the release of cytotoxic granules against a pathogen or infected cells. This can be mediated by antibodies opsonising a pathogen or infected cell and interacting with the cell surface receptor CD16 (FcγRIIIa) on NK cells. Studies suggest that NK ADCC activity plays a role in acquired and vaccine-induced immunity to malaria. This protocol measures ADCC using CD107 as a marker for cytotoxic granule release following incubation with antigen-coated beads or malaria parasites. Briefly, antigen-coated beads or malaria parasites are opsonised by antigen-specific antibodies and incubated with PBMCs and a fluorescently tagged anti-CD107 antibody. Interactions between the Fc-region of antibodies bound in immune complexes and CD16 expressed by NK cells promotes ADCC results in activation of NK cells with granule release and surface expression of CD107. The level of ADCC is assessed by measuring CD107 expression on NK cells (defined as CD3-CD56+ lymphocytes) with flow cytometry.