The subunit protein of the neurofibrillary tangle, the core protein of the neuritic plaque, and the amyloid of the cerebrovasculature in Alzheimer disease and normal aging is a unique 42-amino acid protein (amyloid beta-protein), suggesting a common origin for these pathological entities. However, the expression of the amyloid precursor protein mRNA (APP mRNA) from which the amyloid beta-protein is derived varies between specific neuronal populations. To determine the conditions under which neuronal synthesis of amyloid beta-protein might contribute to the formation of these structures, we have studied the temporal pattern of APP mRNA expression in developing fetal rabbit hippocampal neurons in vitro. Using in situ hybridization with a biotinylated riboprobe transcribed from a cDNA which includes the region encoding the amyloid beta-protein, we have observed a developmentally specific pattern of APP mRNA hybridization during neuronal maturation in vitro.