Monocyte‐mediated‐antibody‐dependent cellular cytotoxicity (MO‐ADCC) was studied in 21 patients with Hodgkin's disease (HD), 15 patients with a long‐lasting remission of HD, 11 patients with non‐Hodgkin's lymphoma (NHL), 11 patients with solid tumors, and 15 normal controls. Lymphocyte ADCC (LY‐ADCC) was evaluated in 12 patients with HD and 9 normal controls. Monocytes and lymphocytes were isolated with cell‐scatter monitored counterflow centrifugation providing high purity and yield. Antibody‐dependent cellular cytotoxicity was evaluated by means of DNA flowcytometry, using antibody‐coated chicken erythrocyte targets (CRBC). in comparison with normal controls MO‐ADCC was significantly increased in HD (P <0.0005), NHL (P < 0.005), and solid tumors (P < 0.005). in patients in a long‐lasting complete remission of HD, MO‐ADCC was in the normal range. Lymphocyte‐ADCC of 12 patients with HD was similar to that of 9 normal controls. in all experiments LY‐ADCC was invariably lower than MO‐ADCC of the same donor, indicating the monocyte as the most potent effector cell towards CRBC targets. Results indicate the following: (1) purified cell suspensions of both lymphocytes and monocytes are essential to unravel their role as effector cells; (2) LY‐ADCC in HD is similar to normal controls; (3) MO‐ADCC enhancement is not uncommon in malignant lymphoma and several solid tumors; (4) normal MO‐ADCC in a group of successfully treated patients with HD suggests a disease‐related induction of enhanced MO‐ADCC.