Common variable immunodeficiency (CVID) is characterized by defective B cell maturation and antibody formation resulting in low serum antibody levels of most or all Ig isotypes. A specific subgroup of patients ("type A") has normal numbers of mature surface (s)IgM / sIgD‐ positive circulating B cells. However, since these lymphocytes do not respond to in vitro stimulation by differentiation and Ig synthesis, they seem to suffer from so far unknown intrinsic defects. Analyzing the expression pattern of a large set of B cell activation‐specific surface markers, we found that type A CVID patients show a highly reduced expression of the CD28 / CTLA‐4 ligand CD86 (B7‐2) and of the lymphocyte activation marker CDw137 when compared to B cells of healthy donors and non‐type‐A CVID patients. The lowered CD86 expression levels were found to correlate with reduced levels of CD86 mRNA. Since combined stimulation via B cell antigen receptor and CD40 cross‐linking did not rescue the defects in CD86 and CDw137 expression, B cells of CVID type A patients resemble functionally unresponsive lymphocytes incapable of cooperating with T cells. The fact that these cells accumulate in type A CVID patients suggests a causal relationship with the pathogenesis of this disease.