Abnormalities in hematologic parameters, associated with prolonged utilization of intravenous fat emulsion (IVFE), were observed in seven children on long-term cyclic total parenteral nutrition (TPN). All patients were receiving IVFE (Intralipid 20%) 1 to 2 g/kg/24 hr as part of TPN, during 3 to 18 months. Recurrent thrombocytopenia occurred in all seven patients. Platelet lifespan, as measured with 111 Indium was reduced. Sea-blue histiocytes containing granulations and hemophagocytosis were seen on bone marrow smears. Scans taken after injection of autologous erythrocytes labeled with technetium-99 showed bone marrow sequestration of these cells. Taken together, this constellation of hematologic abnormalities suggests that long-term IVFE administration induces hyperactivation of the monocyte-macrophage system.