Previous investigations have shown that cerebrospinal fluid from Alzheimer's disease patients contains antibodies that recognize the amoeboid microglia--a nascent and active form of microglia in the developing rat brain [McRae et al. (1991) Neuroscience 41, 739-752]. The present study extended this to show that the same cerebrospinal fluid from Alzheimer's disease patients also labeled the activated microglia and macrophages induced experimentally in adult central nervous system. Thus, in the spinal cord, activated microglia were elicited following the destruction of the motor neurons by the toxic lectin, Ricinus communis agglutinin, injected into the sciatic nerve. The activated microglia which were closely associated with the soma of the degenerating neurons were intensely immunostained with the cerebrospinal fluid from Alzheimer's disease patients. The labeling pattern was comparable to some known monoclonal antibodies including OX-42, OX-18 and OX-6 that mark microglia. The microglia cells on the contralateral normal side remained unstained. In the cerebrum, activated microglia and neural macrophages were induced following an epidural application of the excitotoxin, kainic acid or cryolesion. Immunoelectron microscopy of these cells showed that the immunoreactivity was localized at the plasma membrane and its derivatives suggesting that these are the sites where the antigens are associated. The results obtained in this investigation suggest that these experimental models may be a means to gain further insight to antigens recognized by antibodies in the cerebrospinal fluid of Alzheimer's disease patients.