Host responses during pneumonic pasteurellosis were compared in sheep infected with strains of Mannheimia (Pasteurella) haemolytica A1 differing in their O-antigen type. Nine-week-old, specific pathogen-free lambs were infected intratracheally with parainfluenza type 3 virus (108 TCID50) followed 7 days later by 5—6 . 107 CFU of M. haemolytica A1 possessing rough (group R, 6 lambs) or smooth (group S, 6 lambs) lipopolysaccharide, or saline (group C, 4 lambs). Group C lambs remained afebrile with no evidence of endotoxaemia or bacteraemia and biochemical parameters were normal. Group R and group S lambs became febrile within 2—3 h postinfection and the response was higher and more prolonged in group R lambs. Four group R and 2 group S lambs developed clinical pneumonic pasteurellosis within 24—48 h and the severity of disease correlated with episodes of endotoxaemia, bacteraemia and elevated eicosanoid concentrations. At postmortem, M. haemolytica (107—109 CFU/g) was isolated from the lungs of all 6 group R lambs but from only 1 group S lamb. The results indicate an association between the incidence and severity of ovine pneumonic pasteurellosis and LPS chemotype and suggest an important role for LPS chemotype in determining host-species susceptibility to lung infection.