The levels of expression of messenger RNAs of the 695 and 751 amino acid isoforms of the β-amyloid protein precursor in the brains of three-year-old and 17-year-old cynomolgus monkeys (Macaca fascicularis) were visualized and quantified by in situ hybridization histochemistry using 3 5 S-labelled oligonucleotide probes. The analysis was carried out on coronal brain sections taken through the hippocampus and thalamus at the level of the geniculate nuclei. High densities of β-amyloid protein precursor 6 9 5 and β-amyloid protein precursor 7 5 1 messenger RNAs were found in the medial aspects of the mediodorsal, centromedian and parafascicular nuclei of the 17-year-old monkeys. The messenger RNA levels of the 695 and 751 isoforms were about two- and seven-fold, respectively, those found in the same nuclei of the three-year-old animals. The levels of these messenger RNA transcripts in the 17-year-old monkeys were not significantly different from those in the three-year-old animals in other brain areas e.g. the temporal cortex, entorhinal cortex and hippocampus. No Alzheimer's disease-like neuropathology in terms of diffuse or senile β-amyloid plaques, dystrophic neurites or neurofibrillary tangles were detectable by specific innumohistochemical procedures in the above thalamic nuclei of the 17-year-old animals. In addition no reactive gliosis was seen in the thalamus of these monkeys.The presence of increased levels of β-amyloid protein precursor 6 9 5 and β-amyloid protein precursor 7 5 1 messenger RNAs and the absence of any Alzheimer's disease-like pathology in the thalamus of the middle-aged monkeys may suggest that enhanced transcription of the β-amyloid protein precursor gene may precede by many years any manifestation of the β-amyloid protein accumulation/deposition. The data obtained in the thalamus of the 17-year-old monkeys may be indicative of early molecular events associated with the aging process.