Hanna, Edgar E. (University of Minnesota, Minneapolis), and Dennis W. Watson. Host-parasite relationships among group A streptococci. III. Depression of reticuloendothelial function by streptococcal pyrogenic exotoxins. J. Bacteriol. 89:154-158. 1965.-Measurement of the rate of clearance of colloidal carbon from the circulating blood is an effective and simple technique for assessing the functional state of the reticuloendothelial system (RES) of experimental animals. This paper concerns a study of the RES function in rabbits after treatment with streptococcal pyrogenic exotoxins. Intravenous injection of 1.0 ml of the toxin produced by a strain of type 18, group A streptococcus caused a prolonged (at least 24 hr) depression of RES function. The activity at 48 hr after toxin injection was about equal to that in control animals. Repeated intravenous injections of the toxin abolished the initial depressing effect on RES function, but did not cause stimulation. In comparison, intravenous injection of equivalent doses of endotoxin prepared from Escherichia coli COO8 also caused an initial depression of RES function; however, in contrast with the effect of exotoxin, stimulation occurred as early as 24 hr and was about twice as active at 48 hr. The prolonged depression by streptococcal pyrogenic exotoxin is suggested as one means by which this toxin potentiates lethality and tissue damage by other toxins such as streptolysin O and endotoxins from gram-negative bacteria.