A patient with Whipple's disease developed massive and irreversible CNS involvement after a drug-induced intestinal remission. The multifocal brain lesions were apparent grossly with the heaviest concentration being noted in rhinencephalon, diencephalon, and mesencephalon. This patient exhibited progressive neurologic deterioration, although viable organisms could not be identified in the brain at autopsy. Astrocytes, pericytes, and choroid plexus cells attempted to dispose of the organism, in addition to the traditionally implicated microglial and ependymal cell. © 1979 Springer-Verlag.