Monocytes constitutively express Fc receptor (FcR) for IgG type I (CD64) and type II (CD32), but not type III (CD16). Prior studies have indicated that in vitro culture of monocytes results in spontaneous induction of CD16, but this phenomenon has been variable and the mechanism unexplained. Here, we demonstrate that activated platelets are responsible for induction of CD16 on monocytes, as a consequence of TGF-beta release. Local release of TGF-beta by activated platelets at sites of tissue damage may induce CD16 on infiltrating or resident monocytes that in turn facilitate the function of these effector cells. The FcR on these CD16+ monocytes is functionally competent, and enables the monocytes to kill murine anti-CD16 hybridoma cells. CD16 expressed on platelet-activated monocytes is structurally similar to the transmembrane-anchored CD16-II polypeptide expressed on natural killer (NK) cells. However, whereas CD16-II on NK cells is co-associated with CD3 zeta, we were unable to detect CD3 zeta transcript or protein in monocytes. Transcripts for the gamma subunit of the high-affinity IgE FcR (Fc epsilon RI-gamma) were detected in monocytes, and presumably gamma proteins are co-associated with CD16-II in these cells. Nucleotide sequence analysis of Fc epsilon RI-gamma cDNA derived from both NK cells and cultured monocytes indicated identity with the structure previously cloned from basophils. Since CD16+ monocytes can kill anti-CD16 hybridoma cell targets in the absence of CD3 zeta, these results indicate that CD3 zeta is not essential for signal transduction in CD16-II-mediated cytotoxicity.