We have measured the absolute numbers of EBV-infected B cells in the peripheral blood of healthy persistently infected individuals. Single measurements on a panel of 15 healthy individuals demonstrate that the frequency varies over a wide range from 1-50 per 10(6) B cells. Repeat measurements over 1-3.5 years on several individuals whose frequencies varied over a 10-fold range showed that the variation does not represent the fluctuation in the frequency that can occur within an individual; rather, the frequencies are specific to the individual. The frequency within an individual measured over time is stable and contributes less than 10% to the variance seen in the whole population. These measurements suggest that the level of EBV-infected B cells is tightly regulated and we propose that the same homeostatic mechanisms that regulate the levels of normal B cells also regulate B cells latently infected with EBV.