• When cultured skin fibroblasts were exposed to culture conditions designed to favor the expression of neuronal antigens, cells from each of 19 patients with Alzheimer's disease reacted immunocytochemically with antibodies to paired helical filaments, Alz-50, or both compared with only a small fraction of cells from 19 identically treated age-matched control cultures. Immunoblots confirmed the presence of soluble material reacting with Alz-50 antibody in the Alzheimer fibroblasts. Ultrastructurally, fascicles of 10-nm filaments were seen that occasionally twisted around each other, but no structures were seen that were identical to paired helical filaments. Thus, cultured skin fibroblasts from patients with Alzheimer's disease developed greater immunocytochemical reactivity with antibodies raised to paired helical filaments than did fibroblasts from control subjects, when cultured under the specified conditions.