We examined whether priming monocytes (MO) with Lipopolysaccharide (LPS) influenced their further differentiation into either macrophages (M phi) or dendritic cells (DC), UPS-primed MO differentiated into M phi when cultured further with M phi colony-stimulating factor (M-CSF) but, if cultured then with gramulocyte/M phi (GM)-CSF and IL-4 (interleukin-4), only about 30% of the cells differentiated into CD1a(+)CD14(-) DC and half became CD1a(-)CD14(+) M phi. Cytokines present during LPS priming could affect subsequent MO differentiation. Relative to priming with LPS alone, adding M-CSF to LPS did not modify differentiation of MO to M phi in further culture with RI-CSF, nor did it change the way of differentiation of MO into DC was altered if culture was later switched to GM-CSF/IL-4. Using GM-CSF/IL-4 plus LPS upon priming did not modify differentiation of MO to M phi in further culture with M-CSF, as compared to priming with GM-CSF/IL-4 alone, but it counteracted the effect of LPS on the differentiation of MO to DC in further culture with GM-CSF/IL-4: about 75% of cells then became DC. Alternatively, despite activation by LPS, mature M-CSF-induced M phi preserved the potential to differentiate into DC on subsequent culture with GM-CSF/IL-4. Thus, LPS, a bacterial product known to sustain maturation of MO/M phi as well as of DC, may block the differentiation of MO into DC, except if signal triggering DC differentiation is delivered concomitantly, and modulate in this manner the induction of adaptive immune responses to infection.