To investigate if Alzheimer paired helical filaments (PHF) closely resemble twisted ribbons, as indicated by recent high-resolution ultrastructural studies, we compared physical models of twisted ribbons with electron microscopic images of PHF. Uranyl-acetate-stained, isolated PHF with one or two helical turns were compared with scale models of twisted ribbons with one and two helical turns rotated at different angles. The various rotations of the twisted ribbon model corresponded well with the different orientations of randomly dispersed PHF. The electron-dense regions of individual PHF turns previously thought to represent a cross-over site of paired filaments corresponded to the edge of the twisted ribbon when the ribbon was oriented perpendicular to the filament axis. These data indicate that the overall configuration of PHF is a twisted ribbon but does not exclude possible configuration restrictions due to an ordered arrangement of subunits.