Initial tests for oncologic disease failed to yield a definitive diagnosis, so I next consider an infectious process. Because both the liver and spleen are integral parts of the reticuloendothelial system, the most likely cause of organomegaly in children is an inflammatory response to a systemic infection. Hepatosplenomegaly is commonly associated with many systemic viral infections, including acute Epstein-Barr virus or cytomegalovirus infections, viral hepatitis (hepatitis A, B, C, etc) and HIV. Although lymphocytosis is often seen with acute viral illnesses, many viral illnesses can cause some transient suppression of bone marrow activity, particularly with transient leukopenias. Statistically, viral infections are the most likely cause of infections in children. Bacterial infections can also cause hepatosplenomegaly, both by activation of the reticuloendothelial system and via phagocytosis of organisms and macrophage engorgement. Both processes may be involved to varying degrees by entities such as septicemia, tuberculosis, endocarditis, cholangitis, bartonellosis, and brucellosis. Bacterial sepsis can present with leukopenia or leukocytosis, although I find that leukopenia is both more common and a graver prognostic sign in infants than in older children. Less common infectious causes of hepatosplenomegaly in North America are parasitic (eg, toxoplasmosis or malaria) and fungal (eg, histoplasmosis or disseminated candidiasis) infections, which can present with acute, chronic, or subacute symptoms.