The monoclonal antibody 3C3 reacts with human Toll-like receptor 4 (TLR4, CD284). TLRs belong to a family of proteins that specifically recognize and sense microbial products. They are highly conserved throughout evolution. In Drosophila, toll is required for the anti-fungal response, while the related 18-wheeler is involved in antibacterial defences. TLRs identified as type I transmembrane signalling receptors act as innate immune recognition receptors against many pathogens. TLR4 is a functional receptor for gram-negative bacterial lipopolysaccharides (LPS). TLR4 associates with MD-2 which is absolutely required for LPS-induced activation of TLR4. TLR4 has been identified next to MD-2 and CD14 as a receptor that is central to the innate immune response to LPS of Gram-negative bacteria. The monoclonal antibody 3C3 is a TLR4 function-blocking antibody that is useful for studies on the role of TLR4 as a receptor for LPS induced cytokine production by TLR4 bearing cells.