Peptidoglycan is responsible for the endotoxin-like properties of the streptococcus cell wall. The pyrogenic response of rabbit to group A streptococcus peptidoglycan prepared by hot formamide or TCA is dose-dependent and is increased if the material is ultrasonically solubilized. The pyrogenicity can be eliminated by the antiserum to the peptidoglycan or by the degradation of the material by lysozyme. Peptidoglycans prepared from cell walls of group B and L streptococci, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pneumoniae produce fever effects comparable to the response after group A streptococcus peptidoglycan. Spirillum serpens and Escherichia coli contain in addition to endotoxin the peptidoglycan which is also pyrogenic. Repeated injections of bacterial peptidoglycan to rabbit result in tolerance to the fever effect. Cross-tolerance was recorded only exceptionally. Rabbits tolerant to endotoxin respond with a lower fever to S. aureus and group A streptococcus peptidoglycans. Intravenous administration of peptidoglycan to rabbit causes extensive alterations in the heart characterized by various stages of the degenerative and necrotic process. Local Shwartzman reaction can be elicited in rabbit by peptidoglycan used either as a preparative or as a provocative dose in combination with endotoxin, or it can be used for both doses. The results obtained with peptidoglycans prepared from various bacteria are fully comparable. Non-specific resistance of mice to infection induced by streptococcus cell walls was found to be dependent on the peptidoglycan activity; cell wall proteins and polysaccharide are inactive. These properties of peptidoglycan resemble those known from endotoxin studies. The data presented suggest the role of peptidoglycan in pathological reactions resulting from host-parasite interaction.