Nucleolar volume was measured in nerve cells of the temporal cortex in cases of Alzheimer's disease, obtained at both biopsy and autopsy. Measurements were made on those nerve cells containing neurofibrillary tangles and also on ones free of such changes. Results showed that nucleolar volume is significantly reduced, by at least 40%, in both tangle and non-tangle bearing cells, in both biopsy and autopsy cases, when compared with corresponding values from appropriate control cases. Furthermore, in the autopsy cases, nerve cell nucleolar volume was reduced by a further 30% in tangle bearing cells compared to non-tangle bearing neighbours. No such difference was noted in these cells in the biopsy cases. These findings imply that alterations in protein synthetic capability occur in nerve cells early in the course of Alzheimer's disease, and that this change is not, at least in these initial stages, related to accumulation of neurofibrillary material within the cell body, although later on such accumulation may result in added disruption of cell metabolism.