All reported clinical characteristics of acute retroviral illness with the human immunodeficiency virus (HIV) are nonspecific. Signs and symptoms described are associated with a variety of acute infections. We report the cases of three patients in whom the acute retroviral illness was characterized by transient oral candidiasis and unexplained high lactate dehydrogenase values, with or without transient pulmonary infiltrate, in the context of an acute febrile illness. The clinical findings correlated with a severe reduction in the number of CD4 cells. We believe that thrush could be a marker of acute retroviral infection, as it is not a feature of any other heterophil-negative mononucleosis-like syndrome. We propose that in any patient having transient thrush and acute viral syndrome, the possibility of HIV infection should be aggressively pursued serologically, regardless of the patient's HIV risk status, provided that the usual causes of candidiasis (eg, diabetes mellitus, antibiotic use, and dentures) can be excluded.