Insect Toll and the Toll-like receptors (TLRs) are transmembrane signal transducing proteins that play critical roles in both immunity and development. They are orthologous to mammalian TLRs, all of which have been implicated in immunity (Beutler, 2004) . In Drosophila , the Toll signalling pathway is enacted when the cytokine-like molecule Spaetzle binds to the extracellular domain of the transmembrane receptor Toll. The Drosophila genome encodes a family of six Spaetzle-related molecules, that are believed to function as ligands for the nine Drosophila Toll receptors (Parker et al ., 2001) . Two plausible Spaetzle orthologues are evident in the bee genome (GB15688 and GB13503; Fig. 1 ), and functional tests will be needed to determine which act as Toll-binding cytokines. Following conformational changes of the activated receptor, several intracellular death-domain (DD) containing proteins are recruited to form a receptor complex. Activation of this complex leads to the degradation of the NF kappa B inhibitor (I κ B) Cactus and subsequent nuclear translocation of the NF-κ B transcription factor Dorsal (or the Dorsal-related immune factor, Dif, in Drosophila (Royet et al ., 2005) . Two homologues of Dorsal were found in the honey bee genome (Fig. 1) , neither of which was orthologous with Dif. This lends support to the view that Dif is a highly derived branch found in brachyceran flies but absent from other insects. In mosquitoes (Shin et al ., 2005) , and arguably honey bees, Dorsal (called REL1 in mosquitoes) is a functional alternate for Dif. Functional tests can help determine which of the two dorsal paralogues is the key transcription factor for this pathway. The intracellular components Tollip, Pellino, Cactin and TNF receptor associated factor-2 (TRAF-2) are believed to aid the main players of this pathway, and all appear to be present in both fly species as well as the honey bee. Candidate effectors for the immune-related Toll pathways in honey bees include a compliment of antimicrobial peptides, the melanizing agent phenoloxidase and three lysozymes. While it has not been confirmed that these effectors are triggered by the Toll pathway as opposed to other pathways described below, it is evident that some of the bee effectors are responsive to pathogens and/or mechanical wounding of bees (Fig. 3) . Candidate honey bee members for the Toll pathway. Names are given for the Drosophila pathway components, along with vertebrate orthologues (in parentheses). Honey bee matches given as named during the genome project. Honey bee names in italics refer to genes with close paralogues which cannot readily be distinguished with respect to pathway components from Drosophila. Underlining indicates genes shown to be transcriptionally up-regulated after immune challenge.