Although gross abnormalities have been described in the brains of patients with Down's syndrome (DS), microscopic studies have revealed only minor and inconsistent findings. We compared two DS brains, in whole-brain serial sections, with similarly prepared age- and sex-matched normal controls. Architectonic abnormalities were noted, and cell counts revealed a significant poverty of granular cells in the DS brains, particularly in granular fields such as areas 3,17, and 41. Golgi studies demonstrated all major cell types. A striking feature of the brain morphology in DS may be the curtailment of a specific cell type, most likely the aspinous stellate.