Recently, it has been appreciated that cultured mast cells are significant sources of cytokines. However, the role of interkeukin-1 (IL-1) on mast cells and/or basophil degranulation is still unclear. In this report we provide evidence that rat basophilic leukemia cells (RBLC) cultured with a natural inhibitor of IL-1, interleukin-1 receptor antagonist (IL-1RA) (500 ng/ml) for 48 h, strongly inhibited the spontaneous release of serotonin (5HT) and histamine (from 22.50 to 43.49%), compared to untreated cells (control). When IL-1RA-treated and untreated RBLC were stimulated with a secretagogue (anti-IgE), no difference was found in the percent of 5HT and histamine release. Moreover, in another set of experiments using rat peritoneal mast cells (RPMC) treated and untreated with IL-1RA, we found that IL-1RA did not affect the release of 5HT or histamine, even when the secretagogue anti-IgE or compound 48/80 (C48/80) were used. The present studies describe an additional biological activity of IL-1RA, inhibiting histamine and 5HT release from RBLC cultures.