Mice were infected intranasally with a serotype 2 pneumococcus, a pneumolysin-negative derivative (PLN-A), or an autolysin-negative derivative (AL-2). Numbers of wild type pneumococci were seen in the lung from approximately 12 h after infection and were first detected in the blood around this time. Immunofluorescent staining of lung sections showed that pneumolysin was produced in vivo. Pneumococcal infection resulted in alteration of the composition of the blood but not the bone marrow. Some of the hematologic changes did not occur after PLN-A. PLN-A had a slower growth rate in the lung and bacteremia was delayed. AL-2 was rapidly cleared from the lungs and was not detected in the blood. These events paralleled the pattern of histology in the lung, with the severity of inflammation reduced with PLN-A and no inflammation or hematologic changes with AL-2.