We examined the bone marrow response and the sequestration of polymorphonuclear leukocytes (PMNs) in lung using a bacteremic infection model in rabbits. PMNs were labeled with the thymidine analog 5-bromo-2'-deoxyuridine (BrdU) in the bone marrow, and the bone marrow release and the sequestration of BrdU-labeled PMNs were measured using immunohistochemistry. A focal subcutaneous infection (S) was induced, and the bacteremia (B) was produced 4 h later with Streptococcus pneumoniae (S+B). This S+B group was compared with other groups with only subcutaneous infection or only bacteremia. The S+B group developed a profound leukopenia after the bacteremia that was associated with an increase in circulating BrdU-labeled PMNs. Morphometric studies showed more PMN sequestration in the lung of the S+B group compared with the others (P < 0.05). Compared with unlabeled PMNs, BrdU-labeled PMNs, which represent newly released PMNs, preferentially sequestered in lung (P < 0.05) and were slow to migrate into the infected tissues (P < 0.05). We conclude that bacteremic infection is associated with an accelerated release of PMNs from the bone marrow and that these newly released PMNs preferentially sequester in lung and are slow to migrate into infected tissues.