The beta-amyloid precursor protein is the precursor of the main component of senile plaques (the beta-amyloid peptide or beta/A4) found in the brain of aged humans and, in higher amounts, in the brain of Alzheimer's disease and Down's syndrome subjects. Four different forms of beta-amyloid precursor protein messenger RNAs have been described in humans and rodents: beta-amyloid precursor protein 695, beta-amyloid precursor protein 714, beta-amyloid precursor protein 751 and beta-amyloid precursor protein 770 messenger RNAs (numbers corresponding to the number of encoded amino acids). The two latter forms are characterized by containing in their sequence a region with high homology to the Kunitz family of serine protease inhibitors. We have used oligonucleotide probes to study the distribution of the different messenger RNAs encoding each of the four beta-amyloid precursor proteins by in situ hybridization histochemistry in human, rat and mouse brain. We found that beta-amyloid precursor protein 695, beta-amyloid precursor protein 714 and beta-amyloid precursor protein 751 messenger RNAs were widely distributed in the human, rat and mouse brain and that their distribution was roughly similar in most brain areas in these three species. The distribution of beta-amyloid precursor protein 770 messenger RNA was not so wide and differed among the three species studied. beta-amyloid precursor protein 751 and 770 messenger RNAs were the only forms present at significant levels in rodent choroid plexus and meninges, while beta-amyloid precursor protein messenger RNA isoforms containing and lacking the Kunitz domain were detected in the human choroid plexus. We also observed that the relative levels of beta-amyloid precursor protein 751 and 770 messenger RNAs in the rat cerebral white matter as well as in the mouse and human striatum were higher than those of the beta-amyloid precursor protein messenger RNAs lacking the Kunitz domain. While the most abundant beta-amyloid precursor protein messenger RNAs in the brain of all three species under study were, in descending order, beta-amyloid precursor protein 695 and beta-amyloid precursor protein 751 messenger RNAs, the least abundant form was not the same for all species: in human it was beta-amyloid precursor protein 714 messenger RNA and in rat and mouse brain it was beta-amyloid precursor protein 770 messenger RNA. Our results show differences both inter- and intraspecies of the relative abundance and distribution of four beta-amyloid precursor protein messenger RNAs in rat, mouse and human brain.(ABSTRACT TRUNCATED AT 400 WORDS)