Patients frequently visit ambulatory care settings with acute human immunodeficiency virus (HIV) seroconversion illness, but the illness is often misdiagnosed. This acute viral syndrome, or seroconversion illness, occurs after initial exposure to the HIV virus; it is often resolved before the development of HIV-specific antibodies. Primary HIV infection refers to the 12 months following infection; it includes an acute time period after exposure when routine HIV antibody testing is negative. Primary HIV infection is recognized with the help of a detailed screening history. Diagnosis is confirmed through laboratory tests that detect virus presence. The accurate diagnosis of primary HIV infection can have a beneficial effect on the patient's clinical course and also on public health prevention efforts.