Several studies have shown that interleukin-8 (IL-8) causes a rapid granulocytosis with the release of polymorphonuclear leukocytes (PMN) from the bone marrow (BM) partially responsible for the granulocytosis. This study was designed to quanti tate the release of PMN from the BM by IL-8 and measure the transit time of PMN through the marrow after IL-8 administration, The thymidine analogue, 5'-bromo-2'-deoxyuridine (BrdU), was used to label dividing PMN in the marrow and follow their release into the circulation after intravenous IL-8. This allowed us to calculate the transit time of PMN through the mitotic and postmitotic pools of BM. BrdU was infused intravenously into rabbits 24 hours before IL-8 (2.5 mu g/kg). IL-8 caused a rapid, transient granulocytopenia (5.9 +/- 0.4 at baseline v 0.2 +/- 0.06 x 10/L-9 at 5 minutes, P < .05) followed by granulocytosis (8.4 +/- 0.1 at 30 minutes, P < .05) associated with an increased number (0.3 +/- 0.1 at baseline v 1.2 +/- 0.6 x 10(9)/L at 30 minutes, P < .05) and percentage of band cells (P < .05), as well as a rapid increase in the number of BrdU-labeled PMN (pMN(BrdU)) ill the circulation (0.09 +/- 0.05 at baseline to 1.5 +/- 0.6 x 10(9)/L at 60 minutes, P <,05). The transit time of PMN through both the mitotic and postmitotic pools of BM was not affected by IL-8. To determine the marrow compartment from which the PMN were mobilized by IL-8, we quantitated PMN movement from the hematopoietic and sinusoidal compartments irate the circulation. The fraction of pMN(BrdU) in both compartments was higher than in the circulating blood (P <.05) and the fraction and number of pMN(BrdU) ill the sinusoids decreased with IL-8 treatment (P < .05). We conclude that the pool of PMN residing in the BM venous sinusoids are rapidly released into the circulation after administration of IL-8, (C) 1998 by The American Society of Hematology.