The role of FcαRI (CD89) in PMN-mediated ADCC was investigated by using Fc receptor-blocking antibodies in NIP-IgA2–mediated ADCC against SK-BR–3 cells (A) and in reverse ADCC against HB58 target cells (B). Significant inhibition of ADCC was observed with antibody My43 to FcαRI, but not with antibodies 197, IV.3 or 3G8 to FcγRI, FcγRII, or FcγRIII, respectively. Data from four experiments are presented as mean ± SEM of % specific inhibition. For reverse ADCC assays (B), HB58 hybridoma cells were selected for high membrane expression of their surface immunoglobulin, which is directed against mouse κ light chain, leading to sensitization of targets in the presence of murine antibodies against potential cytotoxic trigger molecules on PMN. In these experiments, PMN were effective with FcαRI or FcγRII-directed antibodies, but not with antibodies to FcγRI or FcγRIII. Results from five experiments are presented as mean ± SEM of % specific lysis. Significant (P < .05) inhibition (A) or reverse ADCC (B) is marked by an asterisk (*).