Although there is substantial evidence that pneumolysin is an important vir
ulence factor in pneumococcal pneumonia, relatively little is known about h
ow it influences cellular infiltration into the lungs. We investigated how
the inability of mutant pneumococci to produce pneumolysin altered the patt
ern of inflammation and cellular infiltration into the lungs. The effect on
bacterial growth in the lungs also was assessed. There were three phases o
f growth of wild-type bacteria in the lungs: a decline followed by a rapid
increase and then stasis or decline. The absence of pneumolysin was associa
ted with a more rapid early decline and then a much slower increase in numb
ers. The pattern of inflammatory-cell accumulation also had distinct stages
, and the timing of these stages was influenced by the presence of pneumoly
sin. Neutrophils began to accumulate about 12 to 16 h after infection with
wild-type pneumococci, This accumulation occurred after the early decline i
n pneumococcal numbers but coincided with the period of rapid growth. Follo
wing infection with pneumococci unable to make pneumolysin, neutrophil infl
ux was slower and less intense. Coincident with the third stage of pneumoco
ccal growth was an accumulation of T and B lymphocytes at the sites of infl
ammation, but the accumulation was not associated with an increase in the t
otal number of lymphocytes In the lungs. Lymphocyte accumulation in the abs
ence of pneumolysin occurred but was delayed.