Intercellular adhesion molecule-1 (ICAM-1) was localized immunohistochemically in postmortem brain tissue of Alzheimer's disease (AD), progressive supranuclear palsy, amyotrophic lateral sclerosis, Pick's disease, and controls. In controls, only capillaries were stained for ICAM-1. In affected areas of neurologically disease brains, a subset of reactive astrocytes was also strongly stained. In addition, there were irregular, diffuse patches of positive staining in the tissue matrix. In AD, many of these patches had dense cores which corresponded with senile plaques. Double immunostaining for glial fibrillary acidic protein and ICAM-1 indicated that some reactive astrocytes at the periphery of senile plaques were positive for ICAM-1. Within such plaques, microglial aggregates were stained intensely for leukocyte function-associated antigen-1 (LFA-1), the adhesion molecule for ICAM-1. The LFA-1/ICAM-1 system appears to play an important role in the interaction of astrocytes and microglia in several neurological diseases.