It is well established that cytokines may influence biological functions of mature mast cells. The aim of our study was to determine the capacity of TNF, IL-4 and IL-6 to induce direct mediator release from rat peritoneal mast cells as well as the action of these cytokines on mast cell secretory activity. We have found that these cytokines did not activate rat mast cells to histamine secretion. However, we have noticed that TNF, IL-4 and IL-6 caused statistically significant decrease of spontaneous histamine release from mast cells. Moreover, we have also stated that the treatment of mast cells with TNF significantly inhibited compound 48/80 - and ConA-induced histamine release. The preincubation of mast cells with IL-4 caused significant decrease of rat mast cell reactivity to stimulation with compound 48/80, and IL-6 treatment practically did not exert any effect on mast cell releasability to activation with compound 48/80, ConA or anti-IgE. These results indicate that TNF, IL-4 and IL-6 may modulate mast cell secretory activity.