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COVER: Recognition by toll-like receptors. Toll-like receptors may recognize microorganisms or microbial toxins, such as endotoxin, sometimes referred to as pathogen-associated molecular patterns (PAMPs), and thus discriminate non-self from self, as illustrated at the top of the figure. Toll-like receptors may also recognize endogenous agonists or "danger-associated molecular patterns" (DAMPs) generated by infection or injury to cells. This mechanism, illustrated in the middle, does not discriminate non-self from self but rather discriminates "danger" from health. A third mechanism recently proposed involves active suppression of the function of toll-like receptors and signaling under conditions in which suppression is released. This conditional model, illustrated at the bottom, shows how toll-like receptors are utilized for development, physiologic processes, as well as host defense and to utilize endogenous or exogenous agonists. For more information, see the article by Tang et al., Pivotal Advance: Endogenous pathway to SIRS, sepsis, and related conditions," pages 282-285. Pictured is corresponding author, Jeffrey L. Platt.