A 30-year-old man with underlying Wiskott-Aldrich syndrome, which is a rare X-linked congenital immunodeficiency syndrome characterized by recurrent infections, thrombopenia, eczema and hematopoietic malignancies, presented with bloody diarrhea. Endoscopic and histological evaluation was compatible with ulcerative colitis. Congenital immune defects are paralleled by enterocolitis mimicking inflammatory bowel disease in a substantial number of patients. Despite therapy with prednisolone and 5-ASA compounds, the patient described here experienced a relapse of the colitis twice. Subsequently a JC virus infection of the central nervous system was diagnosed, and he died due to progressive multifocal leukencephalopathy.