The in vitro and in vivo antipneumococcal activities of the main pneumococcal autolysin (LytA) and Cpl-1, a lysozyme encoded by phage Cp-1, were studied. Intraperitoneal therapy with LytA or high-dose Cpl-1 remarkably reduced peritoneal bacterial counts (>5 log10 CFU/ml) compared with those for the controls. After intravenous injection, LytA was the most effective treatment.This research was supported by grants from the Red Tematica de Investigacion Cooperativa Spanish Pneumococcal Infection Study Network (grant G03/103) (Ministerio de Sanidad y Consumo, Spain) and the program COMBACT Nuevas Dianas para Combatir a las Bacterias Patogenas (grant S-BIO-026-2006) (Consejerıa de Educacion, Comunidad de Madrid, Madrid, Spain). L.H. and G.D.P. received scholarships from the Fundacio´n Conchita Ra´bago; M.G. received a scholarship from the Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo, Spain.Peer reviewed