The action of a toxic substance (P-II fraction), extracted from the pedicellariae of Toxopneustes pileolus, on rat mesentery mast cells was studied. P-II fraction (3×10−5-2×l0−3g/ml) caused a dose-dependent degranulation of mesentery mast cells. The degranulation induced by P-II fraction (10−3g/ml) increased with time, while compound 4 8/80 (1μg/ml) caused a more rapid degranulation. These reactions were dependent on Ca2+ and temperature. When glucose (5.5mM) was omitted during the incubation step, the degranulation by P-II fraction was significantly reduced as compared to that of compound 48/80. On the other hand, the degranulation by P-II fraction was effectively potentiated by the addition of glucose (5.5mM), while the effect of compound 48/80 was unaltered. The effect of theophylline, adrenaline and DSCG on degranulation by P-II fraction or compound 48/80 was compared. In both cases, the degranulation was inhibited by these drugs. These results suggest that P-II fraction-induced degranulation differs from that of compound 48/80 in regards to time course and effects of glucose.