Concentrations of C1q, the first subcomponent of the classical complement pathway, were assayed by Western blot analysis of sera and brain homogenates from Alzheimer's disease (AD) and nondemented (ND) control patients. Immunoreactive serum C1q concentrations did not differ in the two groups, whereas AD superior frontal gyrus exhibited nearly 4-fold more immunoreactive C1q than ND superior frontal gyrus. Cerebellar C1q concentrations were significantly lower than those in superior frontal gyrus, and ND cerebellar C1q was lowest of all. Parallel immunohistochemical experiments showed a linkage between the extent of beta-amyloid immunoreactivity or AD pathology in a structure and the extent of C1q immunoreactivity. These data support and extend the hypothesis that complement mediated processes are related to beta-amyloid deposition and may be involved in the pathogenesis of AD.