We studied the ultrastructure of two fractions of paired helical filaments (PHF) from Alzheimer brains separated on sucrose density gradient. Fraction A2 (1M sucrose) contained filaments which were short in length and did not aggregate while those in fraction AL2 (1/1.5 M sucrose interface) were mostly aggregated. By scanning transmission electron microscopy, PHF in fraction A2 had significantly more mass per nm length of filament (107-120 kD/nm) than those in fraction AL2 (79-85 kD/nm), and they were also wider in their maximum and minimum widths but did not differ in their periodicity. Differences in mass and dimensions between two morphologically distinct populations of PHF suggest that a partial proteolysis may be involved in the generation of the aggregated population of PHF. The results suggest that a similar process may be active in the formation of neurofibrillary tangles.