We report the construction of a fusion protein comprising the extracellular domain of myelin oligodendrocyte glycoprotein (MOG) and a truncated version of Pseudomonas aeruginosa exotoxin A (ETA'). The chimeric immunotoxin targeted MOG-reactive B-lymphocytes by binding selectively to the appropriate receptors, leading to internalization and apoptosis of the target cells. The functionality of the immunotoxin was tested on a MOG-sensitive murine hybridoma cell line and ex vivo on freshly isolated splenocytes from transgenic IgH(MOG) mice. These data demonstrate, for the first time, the specific cytotoxicity of a MOG-containing recombinant immunotoxin expressed in bacteria towards MOG-reactive B-lymphocytes.