Recently it has become clear that a reduction of IgD-CD27+ memory B-cells in adult CVID patients correlates with clinical aspects of the disease. However, little is known about B-cell dysregulation in pediatric antibody deficiency. Reference values are essential for the interpretation of B-cell subpopulations in children. We present the clinical and immunophenotypical characterization of 16 children and adolescents with CVID and hypogammaglobulinemia. Reference values for IgD+CD27-, IgD+CD27+ and IgD-CD27+ B-cells in healthy children were established for five age groups. In healthy controls we found a continuous increase in IgD-CD27+ B-cell percentage with age from 1.35-5% of B-cells in the second year of life to 4.1-18.7% in adolescents. Interestingly, in 12/14 antibody-deficient patients memory B-cells are significantly below the age-related 10th percentile. We conclude that the reduction of memory B-cells is a useful additional marker for the detection of children with CVID hypogammaglobulinemia and may contribute to the early presentation.