Members of the Toll-like receptor (TLR) family have been shown to be important in the activation of cells by a variety of microbial ligands. TLRs are thought to mediate the 'recognition event' that follows an encounter between a mammalian cell and a microbial agent. In the case of the response to bacterial lipopolysaccharide (LPS), it is clear that the ability of these cell surface proteins to initiate the events necessary for activation of cells to produce cytokines is dependent upon 'accessory proteins' such as the pattern recognition protein CD14 and the lipopolysaccharide binding protein (LBP). While the role of these proteins in the LPS-specific response is defined, their role in other TLR responses has not been defined, but it is important in understanding these events and, potentially, in designing new therapeutic strategies. Here we report on the role of these proteins in the response to yeast zymosan. The requirements for this response (which unlike the response to LPS is a response to a particulate antigen) and the role of other serum proteins are defined.