Interleukin-8 was originally discovered as one of the first chemokines activating neutrophil granulocytes (neutrophils) after secretion by lipopolysaccharide-stimulated monocytes. A wealth of information has been gathered concerning the intracellular events mediated by interleukin-8 and the role of interleukin-8 in numerous physiologic and pathophysiologic processes. We discuss recent advances in the understanding of the initial intracellular signals elicited by interleukin-8. Detailed investigation of these events has led to the identification of subtle but significant differences in the signal transduction processes evoked by interleukin-8 receptors. In particular, much has been learned concerning differences in the cellular mechanisms leading to desensitization, internalization, and recycling of interleukin-8 receptors, and functional consequences of interleukin-8 receptor diversity are now being unraveled.