The CXC chemokine interleukin-8 (IL-8) has profound hematopoietic activities following systemic administration. It induces the rapid mobilization of cells with lymphomyeloid repopulating ability in mice and of hematopoietic progenitor cells in monkeys. In this paper, evidence is presented that stem cell mobilization in mice requires the functional expression on the β2-integrin leukocyte function-associated antigen-1 (LFA-1). In monkeys, systemic injection of IL-8 is followed by a significant increase in the circulating levels of the matrix metallo proteinase gelatinase-B (MMP-9). Based on these findings, the hypothesis is discussed that mature neutrophils serve as intermediate cells in IL-8-induced stem cell mobilization by the release of proteinases.