A model of invasive Haemophilus influenzae type b disease in rats was used to compare the net in vivo and in vitro multiplication rates of this bacterium. In both the blood of rats and in vitro cultures (fresh rat blood or enriched broth) there was an exponential increase in the number of CFU per milliliter with calculated net mean generation times as follows: sham-operated rats, 82 +/- 39 min (n = 5); asplenic rats, 34 +/- 5 min (n = 13); broth, 26 +/- 4 min (n = 12); rat blood, 24 +/- 1 min (n = 14). Thus, in vivo multiplication of H. influenzae type b can be extremely efficient.