Previous studies have suggested that phorbol ester-activated neutrophils kill both antibody non-coated and antibody cotae K562 target cells. In this report the contriibution of the receptors Fcgamma III (CD16) and CR3 (CD11b/CD18) in the lytic process was investigated. In neutrophils CD16 and CR3 are up-regulated by the phorbol ester up to 4 and 10 times, respectively. As expected, lysis of non-immunized targets is decreased by 50%. In addition, the interaction of CD16 and AB8.28 induces mobilization and increases granule secretion. Surprisingly, the simultaneous binding of Ab8.28 and anti-CR3 OKM1 to neutrophils completely abolishes the lysis of antibody-coated targets. Unlike CD16, CR3 does not possess a functional role and binding of OKM1 to CR3 does not affect cytotoxicity of immunized K562 targest, but it blocks lysis of non-coated target almost completely, indicating a function as adhesion protein for CR3. These studies demonstrate a distinct role of CD16 and CR3 in mediating antibody-dependent and antibody independent cellular cytotoxicity, respectively.