It is currently thought that IL-12, produced by dendritic cells (DC) early after stimulation by bacterial pathogens or lipopolysaccharide (LPS), acts as a pro-inflammatory cytokine bridging the innate and adaptive immune responses. We found, however, that it is only the p40 subunit and not the IL-12p75 heterodimer that is secreted early in copious amounts in response to LPS. Neither naïve T cells, nor a variety of microbial products, were able to induce IL-12p75 production unless the DC were conditioned by the presence of interferon-gamma (IFN-gamma) or by encounter with previously activated T cells. The inability of naïve T cells or of bacterial products to induce IL-12 argues against its early role as the initiator of innate and adaptive immune responses.