Monoclonal antibodies to the A4 amyloid polypeptide were used in immunocytochemical staining of the Alzheimer disease prefrontal cortex. Analysis of the resulting staining patterns allowed us to evaluate the amounts and distribution of amyloid-protein deposits exclusive of other senile-plaque components. Previously unappreciated infra-structural details of amyloid in the Alzheimer disease brain became accessible through computer-enhanced imaging procedures. Four discrete morphologic classes of amyloid deposits were observed and classified as punctate, macular, ring, and ring-with-core configurations. Computer imaging indicated that all four classes of immunostained deposits contain internal gradients of density. The classes were nonuniformly distributed with regard to size and location within cortical laminae. Our results support two separate but complementary hypotheses concerning the molecular neuropathology of Alzheimer disease in the prefrontal cortex. (i) Irrespective of cortical layer or morphology, density-gradient analyses suggest that amyloid deposits are elaborated through molecular and cellular events that may involve diffusion or coalescence of the A4 polypeptide. (ii) The distribution and morphology of prefrontal cortical amyloid deposits may be dependent upon underlying laminar-specific structures of the neocortex.