Recent reports have expanded our understanding of the range of clinical presentations of the acute seroconversion syndrome and of the virologic and immunologic events that comprise acute human immunodeficiency virus (HIV) infection. A growing number of case reports have documented the highly variable, nonspecific manifestations of acute HIV infection, which may mimic a number of other illnesses. Previously, some manifestations of acute HIV infection have only been associated with established HIV disease. Diagnosis of the acute seroconversion syndrome requires not only a high index of suspicion but also persistence, as serial assays for p24 antigen and the development of HIV antibodies may be required for patients who present during the “window” period.