Abstract. The Bloch-Sulzberger syndrome of Incontinentia pigmenti (I. p.) was observed in 3 generations of one family. The grandmother and mother of 3 sisters with I.p. showed solely the typical skin lesions and no associated ectodermal abnormalities.At the age of 2 years the eldest girl with I.p. suffered from encephalitis after vaccination against smallpox. Four months later, having fully recovered, the patient suddenly deteriorated and developed generalized seizures and signs of increased intracranial pressure. She died 12h after right temporal decompression. Neuropathological examination of the brain revealed acute hemorrhagic encephalopathy involving predominantly the white matter and leading to massive edema. In addition, there were residual signs of a perivenous encephalitis in the central and subcortical white matter of the forebrain. Signs of malformation or developmental abnormalities were absent.The second girl with I.p. experienced an afebrile convulsion 3 weeks after the first injection of diphtheria and tetanus toxoid. At the age of 2~4 years, one week after an upper respiratory tract infection, she developed an encephalitis which resulted in severe neurological sequelae.The third girl with I. p. suffered from an afebrile convulsion without proof of encephalitis at the age of 4 months.The pathogenesis of the CNS disorders which are frequently associated with I. p. is not yet known, but the history of neurologic lesions in this family suggests that inflammatory processes may play an important role in their evolution.