CD14 is a differentiation-stage-linked glycosyl-phophatidyl-inositol-linked glycoprotein on human peripheral blood monocytes and tissue macrophages, which functions as a receptor for lipopolysaccharide. Here, the effects of granulocyte macrophage colony-stimulating factor (GM-CSF1 a cytokine with proliferation- and differentiation-inducing properties on myeloid lineage cells, were studied on CD14 expression by peripheral blood cells. GM-CSF down-regulated the membrane expression of CD14 on monocytes while it up-regulated expression on neutrophils. GM-CSF also decreased the spontaneous release of CD14 in monocyte culture supernatants. Down-regulation of CD14 expression and release was accompanied by a decrease in the mRNA transcript for CD14, suggesting that it most likely reflects an effect on the transcriptional level. The functional significance of this phenomenon, and its potential relation to the terminal differentiation of monocytes, are discussed.