X-linked agammaglobulinemia (XLA) is one of the most common humoral immunodeficiencies characterized from childhood by the absence of peripheral B lymphocytes, reduced levels of serum immunoglobulins and recurrent and severe bacterial infections. These characteristics are the result of Bruton's tyrosine kinase (Btk) protein deficiency in peripheral B lymphocytes. In addition to typical XLA, several atypical cases have been recognized, who exhibited mild or even no clinical symptoms, although they were definitely deficient in Btk protein (atypical XLA). In these patients peripheral B lymphocytes and serum immunoglobulins (Igs) are detectable though at a lower level than in normal people. To clarify the discrepancies between the Btk gene mutations and the phenotypes more atypical patients should be examined. In this study we evaluated the cytoplasmic Btk protein in peripheral monocytes of some hypogammaglobulinemia adults by means of flowcytometric analysis. Heparinized venous blood samples were collected from some hypogammaglobulinemia adults. Mononuclear cells were separated from their blood and first reacted with a phycoerythrin-labeled CD14 monoclonal antibody (MoAb) (staining of monocyte membrane). Next, the cells were fixed and permeabilized. And then these permeabilized cells were reacted with an anti-Btk MoAb (staining of cytoplasmic Btk protein) and incubated with a FITC-conjugated goat antimouse IgG1. The double-stained cells were analyzed on a flowcytometer. By means of flowcytometric analysis we diagnosed three hypogammaglobulinemia adults as XLA, who did not show typical clinical progress of XLA. Advancements in diagnostic methods has facilitated a prompt and definite diagnosis of this disease.