The number of nerve cells of locus ceruleus and their nucleolar volume were determined in 63 normally aged individuals and in 41 cases with neurologic diseases. Pathologic alterations, such as a severe nerve cell loss and atrophy with or without extensive neurofibrillary degeneration or Lewy body formation, were generally seen in the nucleus locus ceruleus in Alzheimer's disease, Down's syndrome, dementia pugilistica, Parkinson's disease, and progressive supranuclear palsy, but such changes were only slight in normally aged individuals and minimal in motor neuron disease. Protein synthetic capacity was substantially reduced in the remaining nerve cells of the locus ceruleus, in Alzheimer's disease, Down's syndrome, and dementia pugilistica, but was unaltered in normally aged individuals (even in extreme old age), in motor neuron disease, and in the few remaining cells in Parkinson's disease and progressive supranuclear palsy. It is suggested that the pathologic alterations in the locus ceruleus found in these diseases, in conjunction with changes in the hypothalamus, lead to impairment of mental ability with eventual dementia through disturbance of the function of those pathways regulating homeostasis within the central nervous system.