Few of the cellular components of group A streptococci appear to be directly toxic for animals or humans. Some preparations of M protein produce an immunotoxic effect on human platelets and neutrophils. Cell wall fragments produce a chronic multinodular inflammatory lesion of dermal connective tissue. The peptidoglycan component of cell walls has many of the biological features of endotoxins. The exotoxins of group A streptococci include the erythrogenic toxins (pyrogenic exotoxins) and the cytolytic toxins (streptolysins S and O). The high prevalence of erythrogenic, toxin-producing strains is difficult to reconcile with the epidemiologic behavior of scarlet fever; the variations may be due to quantitative differences in toxin production or to a shift from the early scarlet fever-associated strains that produce A toxin to the currently prevalent strains that produce B and C toxins. Experiments with animals suggest that a positive Dick test and the rash of scarlet fever result not from a direct toxic effect but rather from enhancement by pyrogenic exotoxin(s) of acquired hypersensitivity to diverse streptococcal products. The mechanism of toxigenic phage conversion is not clear. The pyrogenic exotoxins are associated with the enhancement of endotoxin shock and a wide variety of other biologic properties. Streptolysin S is a nonantigenic polypeptide associated with various stabilizing carrier molecules. It lyses a wide range of mammalian cells, influences T lymphocyte functions, and is probably responsible for the leukotoxic property of group A streptococci. Rheumatic fever has been associated with a streptococcal outbreak due to a nonhemolytic (streptolysin S-negative) strain. Streptolysin O is an oxygen-labile (thiol-activated) cytolysin. It is inhibited by nonesterified cholesterol and binds to cholesterol in the membranes of mammalian cells and organelles, an interaction producing ring-like and C-shaped structures demonstrable by electron microscopy. Streptolysin O affects a number of leukocyte functions. It produces profound electrocardiographic changes in experimental animals and toxic effects on pulsating heart cells in tissue culture. The observation that rheumatic fever is not associated with infection of the skin due to group A streptococci has suggested that nonesterified cholesterol in the epidermis may inhibit a toxic effect of streptolysin O, an effect necessary for the development of rheumatic fever.