Streptococcus faecium possess two Beta,1-4 N-acetylmuramidases (MUR1 and MUR2) which degrade peptidoglycan with different specifities. Furthermore, MUR1 can be found in a latent and proteolytically activated form. Penicillin-tolerant derivatives have been obtained containing substantially reduced levels of activated MUR1, and increased levels of activated MUR2. Possible models for the regulation of these enzymes will be tested. Various penicillin-tolerant and -sensitive derivatives will be obtained, characterized and compared to derivatives defective in MUR1, MUR2 or proteolytic activator functions. From these studies we should derive a better understanding of the regulation of autolytic activity in streptococci and clarify a previously proposed relationship between autolysis and antibiotic lethality.