IL-4 induces down-regulation of CD14 expression on human monocytes only when the cells are cultured with serum. In serum-free cultures we failed to down-regulate CD14 by IL-4. Instead of serum, GM-CSF was required as a co-factor to restore the regulatory effect of IL-4 on CD14-expression. After 4 days of culture human monocytes were quantitatively CD14-negative as determined by flow-cytometry. On day 6, high amounts of CD14 molecules were detected in the SUP of these cultures, whereas intracellular immunofluorescence staining revealed no detectable CD14 in cytokine-treated monocytes. Thus, CD14 is lost by down-regulation (as shown by others) as well as by delivery into the medium. We previously hypothesized that dendritic cells may originate from monocytes. Our present finding support that one of the key markers, distinguishing monocytes/macrophages from dendritic cells, can be lost upon physiological stimuli.