We describe a case of histiocytic hemophagocytosis and increase in blasts in the bone marrow after administration of long acting G-CSF (pegfilgrastim) in a 71-year-old man with underlying myelodysplasia. Pegfilgrastim was discontinued, with resolution of the hemophagocytosis and marked decrease in blasts from 30 to 5%. We postulate that pegfilgrastim provided a continuous stimulation of the monocyte/macrophage system, resulting in histiocytic hemophagocytosis. We recommend caution in defining indications for the use of long acting preparations of G-CSF.