The amyloid beta-protein precursor (APP) gene and its products are implicated in the pathogenesis of Alzheimer's disease. The differential expression of APP transcripts may contribute to this process. In the present study, the distribution of mRNAs encoding APP variants has been determined in the brain of three cases of familial Alzheimer's disease (FAD) using in-situ hybridization histochemistry. One FAD case was associated with a mutation in the APP gene. No differences in distribution or quantity of APP transcripts were observed between FAD cases and controls. Overexpression of APP mRNAs is therefore an unlikely explanation for the deposition of the beta-amyloid (beta/A4) peptide in FAD brains.