Low molecular weight pyrogenic exotoxins from group A streptococci, staphylococcus aureus, streptococcus pneumoniae, and Escherichia coli will be studied to elucidate the mechanisms(s) by which the toxins enhance lethal shock and myocardial damage, and alter the host immune system. The toxins utilized may contribute significantly to development of rheumatic fever, acute glomerulonephritis, mucocutaneous lymph node syndrome as well as lethal shock. In addition, the exotoxins may contribute to lympho-proliferative diseases because of their capacities to deregulate the immune system. It is hoped that the studies proposed will contribute also to our understanding of the mechanism(s) underlying other biological properties such as pyrogenicity and alteration of blood-brain barrier permeability. Toxin-tissue receptor interactions and affinities may regulate the biological effects observed.