Multiparameter flow cytometric analysis was performed on the peripheral blood samples from 25 patients with acute infectious mononucleosis. Phenotypic results were matched with those for patients without viral symptomatology. Samples from all patients with infectious mononucleosis exhibited an activated (HLA-DR+, CD38+) CD8+ cytotoxic-suppressor T-cell population with aberrant down-regulation of CD7, and samples from 2 (8%) of 25 patients also showed down-regulation of CD5. The CD8+ cells also were slightly larger than normal T cells by forward scatter characteristics. None of the control samples showed down-regulation of either antigen. Aberrant pan-T-cell antigenic expression is a criterion in the immunophenotypic diagnosis of T-cell lymphoproliferative disorders. Acute Epstein-Barr virus infection should be considered in the differential diagnosis when down-regulation of CD7 is present, especially in conjunction with an activated CD8+ T-cell population.