Soluble cytokine receptors, molecules that can selectively modulate the effects of a single cytokine, have generated great interest both as indicators of disease and as targeted immunotherapeutic agents. However, cellular sources for soluble cytokine receptors are not well characterized and the regulation of soluble receptor production is not clear. We recently found that interleukin 6 (IL-6) induces the expression of membrane-bound interleukin 4 (IL-4) receptors (mIL-4R) in the murine myeloid leukemia M1 cell line. In the present study we show that IL-6 induces the expression and secretion of the soluble form of the IL-4 receptor (sIL-4R) in these cells as well, with the protein accumulating for up to 72 hours in the cell supernatants. This inducible production of sIL-4R protein is accompanied by the induction of mRNA specific for sIL-4R. In mature bone marrow (BM)-derived macrophages sIL-4R expression can be induced by exposure to either IL-6 or interferon-gamma (IFN gamma). The data suggest that myeloid cells exposed to inflammatory stimuli are one possible source for sIL-4R enabling them to modulate the effects of IL-4 on the immune response by the regulated production of the soluble receptor for this cytokine.