Primary infections with EBV are rarely observed after the age of 20. Some individuals even remain seronegative all their lives. Previously, a lack of EBV receptors on B cells of persistently EBV⁻ adults was described as a reason for long‐term EBV‐seronegativity. The present study examined the CD21 receptor status of 20 repeatedly EBV⁻ healthy adults and 32 EBV⁺ volunteers by means of flow cytometry. CD21 molecules on the surface of CD19⁺ B cells were quantified using anti‐IgG‐coated microbeads. The percentage of CD19⁺/CD21⁺ B lymphocytes was slightly lower in the peripheral blood of EBV⁻donors, but the CD21 antibody binding capacity on CD19⁺ B cells showed no significant differences between EBV⁻ and EBV⁺ adults. In vitro studies showed an equally good EBV transformability of peripheral B lymphocytes of EBV⁻ and EBV⁺ donors. Since HLA‐DR was recently described as a co‐receptor for EBV infection of B cells, we also determined HLA‐DRB1 alleles in the EBV⁻group. We found a significant negative association of EBV‐seronegativity with HLA‐DR13 in comparison with 111 healthy blood donors. In summary, a biologically significant lack of the EBV receptor CD21 on peripheral B lymphocytes of persistently EBV⁻ adults was excluded as a reason for long‐term EBV‐seronegativity.