Vesnarinone (3,4dihydro-6-[4-3,4-dimethoxybenzoyl-1-piperazinyl]-2(1 H)quinolinone) is an inotropic agent used for treating congestive heart failure. Its clinical application is restricted because of agranulocytosis as a side effect. To clarify the mechanism of vesnarinone-induced agranulocytosis, I investigated the effects of vesnarinone on ceramide-related cell differentiation and apoptosis in hematopoietic cells, and cytokine secretion in HFL-1 fibroblasts as a model for stroma cells, In HL-60cells, vesnarinone increased cell differentiation assessed by NBT (nitroblue tetrazolium) reducing ability and apoptosis by DAPI (4,6-diamidion-2-phenylindole dihydrocrochloride) staining. It also increased generation of ceramide which has been recognized as a proapoptotic lipid mediator. I also found that both vesnarinone and ceramide significantly inhibited TPA-induced IL-6 secretion from HFL-1 fibroblasts. These results suggest that vesnarinone-induced agranulocytosis is caused by both the inhibition of the growth factor secretion from fibroblasts, and the enhancement of cell differentiation and apoptosis via ceramide signalling in hematopoietic cells.