Pneumolysin-deficient mutant strains of Streptococcus pneumoniae are known to cause less-severe sepsis than wild-type pneumococcal strains that produce pneumolysin. This difference is associated with greater host resistance in mice infected with the pneumolysin-deficient strains. These studies show that the host resistance developed during the first 1 to 2 days after infection,vith a pneumolysin deficient mutant strain is dependent on tumor necrosis factor alpha but is apparently independent of interleukin 1 beta (IL-1 beta) or IL-6. Survival beyond 5 days appeared to depend on the ability of the mice to produce IL-1 beta.