The technique of in situ hybridization with tritiated RNA probes was used to study the expression of the 68 kDa neurofilament (NF68) gene and the superoxide dismutase-1 (SOD-1) gene in the brains of Alzheimer's disease (AD) patients. Messenger RNA (mRNA) for these proteins was localized and quantified in single cells of formalin-fixed, paraffin-embedded sections of 4 pairs of AD and Huntington's disease (HD) brains from patients matched for age at death and autopsy interval. The cerebellar cortex and hippocampal CA1 and CA2 regions were compared in these two groups of subjects, since in AD the CA2 region of the hippocampus and the cerebellum have been found to be relatively unaffected by the Alzheimer process in comparison to the hippocampal CA1 region. The amount of NF68 mRNA was reduced by approximately 50% in pyramidal cells of both the CA1 and CA2 of AD hippocampus (P less than 0.001), and by 15% in the Purkinje cells of AD cerebellum (P less than 0.05) relative to that of the HD individuals. SOD-1 mRNA was reduced by about 22% in the CA1 of AD brains (P less than 0.001) with no corresponding reduction in the CA2, and by only 5% in the AD cerebellum (P greater than 0.5). The paired design of the study suggests that these results are not simply attributable to the effects of autopsy interval or the agonal process in each patient's death.