FcγRIII is a family of protein isoforms encoded by at least two distinct, yet highly homologous, genes. FcγRIII on neutrophils is a glycosylphosphatidylinositol-linked protein with an allelic polymorphism (NA1/NA2) while FcγRIII on NK cells (FcγRIII(NK)) is an exclusively transmembrane protein without the NA polymorphism. The relationship of the isoform of FcγRIII expressed on cultured monocytes (FcγRIII(Mφ) to these two forms, however, is unclear because some evidence suggests lowered expression of FcγRIII(Mφ) in paroxysmal nocturnal hemoglobinuria (unlike FcγRIII(NK)) and a unique deglycosylated m.w. for FcγRIII(Mφ). In this study we demonstrate that, as with FcγRIII(NK), FcγRIII(Mφ) is resistant to the action of phosphatidylinositol-specific phospholipase C and is expressed at normal levels on affected (glycosylphosphatidylinositol-anchor negative) cultured monocytes from patients with paroxysmal nocturnal hemoglobinuria. FcγRIII(Mφ) is also shed from the cell surface upon incubation at 37°C. However, FcγRIII(Mφ) and FcγRIII(NK) have different m.w. as glycosylated proteins despite the same deglycosylated m.w. Thus, each cell type appears to express distinct glycoforms. These differences in glycosylation may influence the functional properties of the receptor.