We observed that differences in the in vivo growth kinetics of pneumococcal strains of capsular types 3, 4, 5, and 6 were reminiscent of differences that we had previously reported for type 2 strain D39 and its pneumolysin-deficient mutant, PLN. Capsular type 2 Streptococcus pneumoniae D39 exhibits exponential growth in the blood of XID mice until the death of the mice at 24 to 36 h. In contrast, PLN reaches a plateau in growth that is maintained for several days. Capsular type 3 and 5 strains exhibited exponential growth and caused rapid death of XID mice following intravenous challenge, similar to the observation with D39. Strains of capsular types 4 and 6 exhibited growth kinetics reminiscent of PLN. Since the observed differences in the pathogenesis of types 3 and 5 compared to 4 and 6 were reminiscent of the effects of pneumolysin deficiency in type 2, we examined the levels of in vitro pneumolysin production for the entire panel of strains. The onset of pneumolysin production in most strains was rapid and occurred near the end of log-phase growth. Differences in in vivo growth patterns of capsular type 2, 3, 4, 5, and 6 strains were not found to be associated with differences in the levels of pneumolysin.