Multisystemic chromatolytic neuronal degeneration, a newly recognized disease of Cairn Terriers, is described in a second affected North American puppy. In this puppy, the early onset of hind limb weakness at 11 weeks and rapid development of signs of diffuse CNS involvement were distinctive. Signs of cerebellar dysfunction were prominent, but bouts of cataplectic collapse in this puppy constituted the most distinguishing clinical feature. Although electroencephalograph (EEG) recordings lacked a true rapid eye movement (REM) pattern during cataplectic episodes, cervical electromyograph (EMG) potentials ceased or diminished, and imipramine injection was associated with arousal. Postmortem studies revealed that chromatolytic degeneration was very widespread, affecting many neuronal populations in the brain and spinal cord as well as neurons in sensory ganglia. Although the pattern of chromatolysis varied among affected perikarya, chromatolysis was consistently related to dispersion and loss of ribosomes. In this puppy, as opposed to six studied previously, thoracolumbar myelomalacia also occurred symmetrically in the dorsal horns and adjoining funicular white matter. The metabolic derangement underlying this chromatolytic neuronal degeneration and myelomalacia remains unknown.