The aim of this study was to measure the levels of B-cell-activating factor (BAFF), a proliferation-inducing ligand (APRIL), and co-stimulatory molecules in immune thrombocytopenia (ITP) of childhood to investigate the interaction between T and B lymphocytes and the impact of proliferation of B lymphocytes in the pathogenesis. Twenty newly diagnosed ITPs, 20 chronic ITPs, and 20 healthy controls between 2 and 18 years were enrolled in this study. Hemogram, BAFF, APRIL, interleukin-4, and interferon (IFN)-γ levels in sera and expressions of CD19, CD 3, CD21, CD40, and CD 154 on leukocytes were measured by ELISA and flow cytometry. Mean BAFF level in newly diagnosed ITP group was higher than the mean BAFF level in other groups. BAFF levels were significantly decreased after the treatment in newly diagnosed ITP group. APRIL, interleukin-4, and IFN-γ in newly diagnosed ITP group and BAFF, APRIL, interleukin-4, and IFN-γ in chronic ITP group were similar before and after treatment. There was no statistical difference for expressions of CD 19 and CD3 on lymphocytes, CD40 on leukocytes, CD154 on T cells, and for percentages of CD21/CD40, CD21/CD40, CD21/CD40 B cells, and CD19/CD3 lymphocytes for pretreatment and posttreatment levels in both ITP groups. In conclusion, our study strongly demonstrated that BAFF has an important role in the pathogenesis of newly diagnosed childhood ITP. It may be important in the follow-up and in novel therapy modalities of these patients.