In rat neutrophils, formyl-Met-Leu-Phe (fMLP)-induced inositol phosphate formation was inhibited by abruquinone A (IC 5 0 value about 32.7 +/- 6.4 μM) as well as by a putative phospholipase C inhibitor, [6-[[17β-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1 H-pyrrole-2,5-dione (U73122) (IC 5 0 value about 11.3 +/- 1.2 μM). The reduction in inositol phosphate levels appeared to reflect inhibition of phospholipase C activity because the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP 2 ) catalyzed by a soluble fraction from neutrophils was also inhibited by abruquinone A (IC 5 0 value about 31.4 +/- 5.6 μM) over the same range of concentrations. Although abruquinone A alone induced Ca 2 + and Mn 2 + influx into neutrophils in Ca 2 + -containing medium, abruquinone A, like U73122, inhibited Ca 2 + release (IC 5 0 value about 23.5 +/- 0.5 μM) from internal stores in Ca 2 + -free medium. These results indicate that abruquinone A inhibits the activity of phosphoinositide-specific phospholipase C in neutrophils.