A dose-dependent neutrophil migration was observed following the injection of recombinant interleukin-8 (rIL-8) into rat peritoneal cavities. This finding contrasts with the inability of rIL-8 to induce neutrophil emigration into subcutaneous air-pouches. Pre-treatment of the animals with dexamethasone (0.5 mg/kg, s.c.) or depletion of the peritoneal resident cell population abolished the neutrophil migration induced by rIL-8 and by recombinant interleukin-1 beta (rIL-1 beta). Different from that which occurs with rIL-1 beta, neutrophil migration induced by rIL-8 was not enhanced by an increase in the peritoneal macrophage population. Transference of homologous total resident peritoneal cells to the air-pouch rendered this cavity responsive to the chemotactic effect of rIL-8 and potentiated the neutrophil migration induced by rIL-1. Our results show that both rIL-8 and rIL-1 beta are able to induce in vivo neutrophil migration by an indirect mechanism, dependent on resident cells. Neither macrophages nor lymphocytes seem to be involved in the rIL-8 chemotactic effect. However, peritoneal resident mast cells may be implicated in this mechanism. These cells, when stimulated in vitro by rIL-8, released a factor that when injected into peritoneal and air-pouch cavities induced neutrophil migration.