The neuritic plaque is a characteristic finding in Alzheimer's disease. A major component of the plaque core is a 4.2 kd polypeptide, amyloid beta-protein (ABP), which is derived from the C-terminus of a larger precursor protein (ABPP). The authors have studied the transcription of ABPP mRNA in the adult rat brain by Northern analysis and in situ hybridization, and report that the ABPP gene gives rise to essentially the same multitranscript family of mRNAs as in the human, and that differential transcription patterns exist between brain and kidney. Morphologically, ABPP mRNA is expressed ubiquitously in neurons of the fore and hindbrain. ABPP transcripts also are present less frequently in occasional glial cells and at moderate to low frequency in nonneural cell types, namely, the choroid plexus epithelium, ependymal cells, and leptomeningeal membranes. Neuronal transcripts are most abundant in cerebral cortical layers II and V, the pyramidal cell layer of the hippocampus, the olfactory cortex, nucleus basis pontis, cranial nerve nuclei, and, significantly, in Purkinje cells and cerebellar granule cells. Because the cerebellum is relatively uninvolved in Alzheimer's disease, these findings suggest that high intraneuronal expression of ABPP may be a necessary but not sufficient requirement for plaque formation.