Clinical and laboratory markers of simian immunodeficiency virus (SIV) infection were studied during the first 3 months after intravenous inoculation of rhesus macaques. Virus-binding serum antibody titres were correlated strongly with disease progression (P < 0·005) and were predictive of disease outcome by 7 weeks after inoculation. Low virusbinding serum antibody responses to SIV occurred in animals that also showed acute depletion of circulating CD20 B cells. Acute damage to the CD4 T cell and CD20 B cell populations rendered some animals incapable of mounting virus-specific antibody responses and these macaques became the rapidly progressing cases comprising approximately 20– 30% of infected animal cohorts.