In an X-linked immunodeficiency with hyper IgM (X-HIM), several mutations of genes coding for CD40 ligand are responsible for B-cell defects. However, it is controversial whether the defective class switching from IgM to IgG or IgA but not IgE is rescued by in vitro stimulations or not. In six X-HIM patients, signaling through CD40 induced IgE but not IgG or IgA secretion in vitro. When transferred into SCID mice, however, B-cells of X-HIM patients secreted as much IgG and IgA as those of healthy controls. Moreover, sIgG and sIgA expressions were also induced by the in vivo stimulation. These results support that B-cells of X-HIM patients are defective of in vitro class switching from IgM to IgG or IgA and show that the in vivo stimulations rescue the defective class switching and suggest that the class switching of IgE and that of IgG or IgA might be regulated quite differently.