A 21-year-old man admitted for idiopathic fever and sore throat was diagnosed with virus-associated hemophagocytic syndrome (VAHS) when bone marrow aspirate showed hemophagocytosis. ELISA for HIV antibodies was negative, although HIV RNA was positive. VAHS is extremely rare as an initial manifestation in HIV infection, being reported, to our knowledge, in only 4 subjects in Japan. Hemophagocytic syndrome (HPS) features fever and hepatosplenomegaly associated with pancytopenia, hypertriglyceridemia, and hypofibrinogemia, due to hypercytokinemia. Physicians should thus be aware that primary HWV infection may involve glandular-fever-like illness and should start prompt diagnosis to contain AIDS spread.