Although important in neurodegeneration, systematic studies of nicotinic acetylcholine receptor expression in normal aging human brains are difficult to perform. We have studied the expression of nicotinic receptor alpha 4-1 and alpha 5 mRNA in the frontal and parietal isocortex of 3- (young adult), 24- (late middle aged), and 33-month-old (old) rats by nonisotopic in situ hybridization. In all groups transcripts were mainly present in layer II/III and V pyramidal neurons. The numerical densities of alpha 4-1 mRNA-containing neurons with respect to those of cresyl violet-stained neurons decreased with aging in the rat frontal and parietal cortex, while those of alpha 5 mRNA-containing neurons were not affected. These findings point to an age-related decrease of the percentages of numerical densities of alpha 4-1 mRNA-containing neurons, which has to be taken into account as a possible substrate for the well-known decrease of nicotine binding sites in the aging cerebral cortex.