Serum samples from 128 blood donors were tested for antibodies specific for human herpesvirus-8 by an immunofluorescence assay that detects antibodies against mainly lytic antigens. An overall seroprevalence of 56.25% was found (male donors, 54.68%; female donors, 57.11%). These findings indicate that human herpesvirus-8 infection is hyperendemic in Peruvian blood donors. © 2007 by the Infectious Diseases Society of America. All rights reserved.