The acute retroviral syndrome associated with primary HIV-1 infection is characterized by clinical signs of immune activation, multi-system dysfunction, and high levels of cell-associated and plasma viremia, p24 antigenemia, and proviral burden. Clinical abnormalities associated with acute HIV-1 infection and measures of viral burden and replication generally decline in concert with seroconversion. Despite clearance of virus, patients experiencing severe forms of the acute retroviral syndrome appear to have a poorer prognosis than patients with asymptomatic primary infection. This accelerated natural history may be due to the virulence of strains causing symptomatic infection, sequelae of initial high-titer viremia and consequent high viral burden, or immune depletion through immunopathologic mechanisms accelerated by strong antigenic stimulus in primary infection. Early intervention with anti-retroviral and immune modulatory agents has the potential to alter the natural history of patients with this syndrome.