Antibody-dependent cellular cytotoxicity (ADCC), an important defense against viral infections, is generally measured in 51Cr-release assays. However, the effect of ADCC on viral burden is more relevant in vivo. An assay was developed to determine the impact of antibody and cytotoxic cells on reducing the amount of measles virus cultured from infected cells. Although the components of this assay are the same as those involved in ADCC, the endpoint is a reduction in virus infectivity rather than cytotoxicity. The immune function measured in the assay has therefore been termed antibody-dependent cell-mediated immunity (ADCMI). Measles virus-infected Raji cells and blood mononuclear cells served as target and effector cells, respectively. Effector cells were incubated with antibody-labeled or unlabeled target cells for 24 h, and virus infectivity determined. Adding effector cells to unlabeled target cells reduced virus titer by 81.8%. Labeling target cells with measles-seronegative serum had little further effect. However, labeling target cells with measles-seropositive serum reduced infectivity an additional 96.5%. By allowing serum to remain in the supernatant fluid after labeling target cells, neutralizing and cell-mediated antibody functions were simultaneously measured. Finally, arming cytokine-activated effector cells with measles-seropositive serum also reduced virus infectivity. This novel assay provides an important tool for evaluating the anti-viral effects mediated by antibody and effector cells.