Streptococcus pneumoniae dose response. A–C: mice inoculated intranasally with between 1 × 107 and 1 × 108 cfu of S. pneumoniae developed dose-dependent weight loss, hypothermia, and arterial hypoxemia measured in freely moving mice. Data are means (SD), n = 5 per dosing group; *P < 0.0001 for group, time, and interaction term (group × time) by repeated-measures ANOVA; ^P < 0.0001 for group, P = 0.23 for time, P = 0.0003 for interaction term; #P = 0.0001 for group, P < 0.0001 for time, P = 0.0004 for interaction term. D: severity of lung injury as assessed by pulmonary edema was greatest in the 1 × 108 dose group; % by Mann-Whitney. E: representative low-power photomicrographs showing normal lung, patchy pneumonia 7 days following intranasal inoculation with 3 × 107 cfu S. pneumoniae, and profound lung consolidation with a dense inflammatory infiltrate following inoculation with 1 × 108 cfu S. pneumoniae.