Nigellone is the carbonyl polymer of thymoquinone, isolated from Nigella Sativa L. seeds. The polymer is far less toxic but retains much of the pharmacologic properties of thymoquinone, which is the active principle. Our investigations, carried out on rat peritoneal mast cells in vitro, show that nigellone in relatively low concentrations is very effective in inhibiting histamine release induced by the secretagogues: antigen in sensitized cells, compound 48/80, and the calcium ionophore A23187. The mechanism of action seems to be through decreasing intracellular calcium by inhibiting its uptake and stimulating the efflux, and by an inhibition on protein kinase C. There is also indication for a mild inhibition of oxidative energy metabolism contributing to some inhibition of the release.