Human immunodeficiency virus type 1 (HIV-1) infection has a broad spectrum of clinical manifestations, ranging from asymptomatic seroconversion to a severe symptomatic illness resembling infectious mononucleosis or other medical conditions including hepatitis, meningoencephalitis, or pneumonitis. Without clinical alertness, the illness is usually misdiagnosed or even not considered. Here we report 3 cases of acute HIV-1 infection with either a negative HIV-1 antibody assay or an indeterminate Western blot result, but high plasma levels of HIV-1 RNA. The initial presentations included fever, skin rash, sore throat, neck lymphadenopathy, cough and headache. One patient presented with infectious mononucleosis-like illness, 1 with aseptic meningitis, and 1 with acute tonsillitis. Physicians should be alert to the possibility of acute HIV-1 infection, especially in cases with unexplained fever, lymphadenopathy or rash.