X-Linked Agammaglobulinemia is the prototypical humoral immunodeficiency first described by Bruton in 1952¹. It is characterized by a paucity of circulating B cells and a drastic reduction in the serum concentrations of immunoglobulins²,³. Studies analyzing patterns of X chromosome inactivation showed that the genetic defect was intrinsic to the B-cell lineage,⁴ and mapping studies located the defect in the midportion of the long arm of the X chromosome at Xq22⁵–⁷. Recently, two reports demonstrated that mutations of the cytoplasmic tyrosine kinase gene Btk (the gene for Bruton's tyrosine kinase, previously designated bpk or atk) are . . .