Induction of IL-8 gene expression was investigated in IL-2-stimulated circulating peripheral blood polymorphonuclear neutrophils (PMN). Brief exposure of normal PMN to human rIL-2 enhanced both transcriptional and translational expression of IL-8. The IL-8 mRNA was first detectable by 3 h, followed by a continuous maintenance of high mRNA levels up to 18 h. Maximal transcription was obtained with 1000 U/ml of IL-2, which achieved the level observed with known neutrophil-activating factors such as granulocyte macrophage-CSF and Candida albicans. The protein synthesis inhibitor, cycloheximide, had no detectable effect on levels of IL-8 mRNA expression in PMN incubated in medium alone; however, cycloheximide could selectively modulate IL-8 mRNA transcription in PMN, depending on the cytokine used. Cycloheximide did not affect or alter IL-8 mRNA induction in IL-2-treated PMN but abrogated it in granulocyte macrophage-CSF-treated PMN and super-induced the level of IL-8 mRNA in C. albicans-treated PMN. Of significance was the observation that IL-2 has no direct chemotactic effect on PMN, whereas the cell-free supernatants from IL-2-stimulated PMN show potent chemotaxis for freshly isolated PMN, which can be specifically blocked by anti-IL-8 Abs. These findings suggested that the induction of IL-8 gene expression in PMN by IL-2 may be involved in the recruitment of PMN into tissues during local IL-2 therapy in human cancer and in part contribute to tumor rejection.