Homeostatic mechanisms controlling levels of circulating leukocytes have been an enigma in the field of hematology for decades. The short circulating half-life of PMNs relative to other leukocytic cell types, and their critical role as a front line of defense against infectious agents ascribes particular importance to this regulatory process. While strident advances have expanded our knowledge of how leukocytes develop and mature in the bone marrow, their regulation and mechanisms for transport into the circulation remain largely unexplained. The relatively recent availability of recombinant cytokines and other highly purified biologic mediators, as well as the development of monoclonal antibodies against specific leukocyte adhesion molecules have led to new insights and renewed interest in this dynamic process (Springer, 1990; Petrides and Dittmann, 1990). This article reviews recent advances in defining the cellular and molecular interactions involved in leukocyte recruitment by various mediators, and proposes conceptual models for regulation of circulating leukocyte levels.