Telencephalic white matter of the neonatal kitten frequently contained diffuse astrogliosis or focal necrosis (sometimes including the thalamus and the caudate) following a single intraperitoneal injection of Escherichia coli lipopolysaccharide. No evidence for a disseminated intravascular coagulopathy was found. Telencephalic lesions in neonatal monkey and rabbit were also hemorrhagic. Enhanced karyorrhexis of glial nuclei was present in the telencephalic white matter of the neonatal rat. In the kitten, a delay in the generation of macrophages and hypertrophic astrocytes occurs following transient neonatal endotoxemia. Marked weight loss and temperature fluctuation are prominent systemic effects. Large hemispheric cavitary lesions are not accompanied by obvious neurological deficits in the kitten.