The expression of the human Fc receptor with low affinity for IgG (Fc gamma RIII, CD16) encoded by the Fc gamma RIII-A or Fc gamma RIII-B genes is restricted to natural killer (NK), a subset of T cells and macrophages or neutrophils (PMN). The genetic heterogeneity of Fc gamma RIII generates alternative membrane-anchored proteins with distinct signaling capacities when cross-linked by immune complexes. Of great importance is the characterization of the regulatory gene elements directing the expression of a particular Fc gamma RIII isoform to a given specific cell type. Molecular characterization of the Fc gamma RIII-A and Fc gamma RIII-B genes has revealed that the promoter regions display distinct tissue-specific transcriptional activities. In addition, the differential Fc gamma RIII-A/B gene activation can be regulated by enhancer elements located in the more upstream and intron regions. Transcription initiation in NK cells occurs also outside the normal promoter region by a second independent Fc gamma RIII-A promoter. Analysis of the additional Fc gamma RIIIa2-4 transcripts suggests the expression of novel, as yet unknown Fc gamma RIII receptor isoforms on NK cells.