Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is an attenuated live vaccine that may cause life-threatening clinical disease in children with impaired immunity. In particular, patients with any of the nine known inherited disorders of the interleukin-12/23 interferon-γ (IL-12/23-IFNγ ) axis are highly vulnerable to BCG. We describe two unrelated young Slovakian children suffering from disseminated BCG infection which developed shortly after routine BCG vaccination after birth. During treatment with selected anti-BCG antibiotics, resistance against several of these drugs developed. In both children, interleukin-12/23 receptor β 1 (IL-12/23Rβ 1) deficiency was diagnosed. Thus, in addition to chemotherapy, immunomodulatory treatment with recombinant IFN-γ was performed as the pathogenesis of BCG disease in IL-12Rβ 1 deficiency involves impaired IL-12-and IL-23-dependent IFN-γ production by lymphocytes. One child responded to treatment and is presently doing well whereas the second patient died. Conclusion: The marked variability of outcome of disseminated Bacillus Calmette-Guerin disease in interleukin-12/23 receptor β 1-deficient children sharing the same ethnic origin and exposed to a similar environment as presented in these case reports has to be taken into consideration for diagnosis and treatment of infections due to this genetic defect. Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is an attenuated live vaccine that may cause life-threatening clinical disease in children with impaired immunity. In particular, patients with any of the nine known inherited disorders of the interleukin-12/23 interferon-γ We describe two unrelated young animals from suffering from BCG infection which developed shortly after routine BCG vaccination after birth. During treatment with selected anti-BCG antibiotics, resistance against several (IL-12/23-IFNγ) axis are highly vulnerable to BCG. Of these drugs developed. In both children, interleukin-12/23 receptor β 1 (IL-12 / 23Rβ 1) deficiency was diagnosed. Thus, in addition to chemotherapy, immunomodulatory treatment with recombinant IFN- γ was performed as the pathogenesis of BCG disease in IL-12Rβ 1 deficiency involves impaired IL-12-and IL-23-dependent IFN-γ production by lymphocytes. One child responded to treatment and is presently doing well the the se Cond patient died. Conclusion: The marked variability of outcome of disseminated Bacillus Calmette-Guerin disease in interleukin-12/23 receptor β 1-deficient children sharing the same ethnic origin and exposed to a similar environment as presented in these case reports has to be taken into consideration for diagnosis and treatment of infections due to this genetic defect.