SUMMARY: A bacteriological and histological study was made of the sequence of events in unprotected and protected mice, after intracranial challenge with Bordetella pertussis. No difference in the results was obtained whether mice were injected through the parietal bone or through the foramen magnum. Injected material was distributed throughout the subarachnoid space and ventricles. In unprotected mice organisms multiplied continuously until death. Bacterial multiplication was limited to the cranial cavity, in which it was practically confined to the ciliated layer over the ependyma. There was no invasion of the brain substance. The histological changes in the brain included purulent meningitis, choroiditis, polymorphonuclear infiltration of perivasvular spaces and cerebral substance, haemorrhages, hydrocephalus and necrosis of nerve cells. In protected mice there was a brief initial multiplication of organisms and then their rapid elimination. Histologically the brains of immune mice after challenge were characterized by an intense mononuclear-cell response, which persisted for 2-3 weeks, subsiding slowly during the following 10 weeks.