Chemokines are a family consisting of at least ten distinct novel 8-10 kD cytokines. The cysteine-cysteine (C-C) chemokines are chemoattractant and activators for monocytes, T cells and mast cells. RANTES is the prototype of the C-C chemokine subfamily, purified from different sources with chemoattractant and activator properties. In this study we found that supernatants derived from TNF-alpha (scalar concentrations)-activated rat peritoneal mast cell cultures (5 x 10(5)/mL), incubated overnight, produced high levels of RANTES. This data describes an additional mode of generation of RANTES. Moreover, RANTES mRNA was not significantly produced in untreated cells, while it was dramatically increased by calcium ionophore A23187, LPS and TNF-alpha compared with the controls. These results underscore the importance of the presence of mast cells for the production of RANTES in the inflammatory process and contribute to an understanding of the mechanism by which RANTES profoundly affects inflammatory responses in vivo.