Significant nonendotoxin microbial pyrogens include cellular wall/membrane components from both gram-negative and gram-positive bacteria, fungi, virus, mycobacteria, mycoplasma, and spirochetes, as well as exotoxins from Staphylococcus and Streptococcus, notably enterotoxins from Staphylococcus aureus and exotoxins fromStreptococcus pyogenes. Significantmicrobial constituents capable ofproducing a host response that may include fever are listed in Table 1. The dose (or level of infection) is a determinant of both host activity and pyrogenicity, and the potency of various microbial components vary widely. The entire list of microbial cellular constituents capable of cytokine stimulation in host cells is very large and growing, and no attemptwill bemade tonameordescribe themall.Note that the term“pyrogen” is largely being superseded by terms more in keeping with advances in the understanding of host cell activation and inflammatory response at the cellular level. While “microbial pyrogen” describes a systemic response to levels of biologically active compounds capable of eliciting such a response,many host active compounds have the capability to be pyrogenic if their dose or level of infection is high enough (Chapter 13). Because it is not altogether common for some of themicrobial products discussed in this chapter to reach such levels in humans, given the reasons discussed in Chapter 2 (i.e., growth requirements) except perhaps via infection, they are not historically considered pyrogens. Furthermore, for some the ability to activate macrophage to produce tumor necrosis factor (TNF)-a and other cytokines that are prerequisites to fever has only recently been determined. One must wonder if, in the future, the idea of pyrogenicity [based as it is more in history than in the severity of adverse effects it is intended to signify (1)] will not give way altogether to new tests capable of detecting a broader class of deleterious host modulins [to use the Henderson et al. term (2)].