The CD14 surface molecule is predominantly expressed by cells of myeloid origin and regarded as a specific marker for macrophages (M phi). Thus, in human mononuclear cell preparations, CD14 expression is a widely used parameter to distinguish M phi from dendritic cells (DC). Since a murine homologue of CD14 was recently identified, this study investigated expression of CD14 by murine M phi and DC. Flow cytometry with a monoclonal antibody directed against murine CD14 revealed that bone marrow-derived DC express CD14 to various extents during differentiation. Functionally, CD14high and CD14low DC did not differ significantly in their capacity to present alloantigen, protein antigen or immunogenic peptide. Furthermore, surface expression of CD14 could be modulated by interleukin (IL)-4 and LPS. Incubation of bone marrow-derived DC with IL-4 (100 U/ml) resulted in downregulation of CD14 surface expression, whereas exposure of BmDC to LPS (1 microgram/ml) led to upregulation of CD14. After blockage of CD14 molecules by incubation of DC with anti-CD14 antibodies, downregulation of LPS triggered IL-1 release could be detected. In addition, other M phi markers such as CD11b, F4/80, BM8, and ER-TR9, are also expressed on DC. Therefore, we conclude that CD14, like other M phi markers, is expressed on murine DC during maturation. Thus, M phi and DC cannot be distinguished by flow cytometry using these markers. Moreover, CD14 may be involved in mediating LPS-induced activation of murine DC.