By using single- or double-color immunohistochemistry of β-amyloid peptide, complement proteins C4d, C3d, and C5b-9, and the HLA-DR marker LN-3, differences were detected in the extent of complement activation in the two major types of cerebellar β-amyloid peptide deposit, diffuse and compacted senile plaques. Both types of deposit were highly co-localized with immunoreactivity of complement protein C4d, an early stage complement fragment. However, immunoreactivity of C3d, an intermediate stage complement fragment, co-localized predominantly with compacted plaques and could only occasionally be found in diffuse plaques. Immunoreactivity for C5b-9, the membrane attack complex formed as a final step in full complement activation and responsible for lysis of bystander cells, could only be detected unequivocally in compacted plaques, not in diffuse plaques. The failure of full complement activation in diffuse plaques, which greatly predominate in the Alzheimer's cerebellum, may underlie the relative paucity of cerebellar pathology and clinical symptomatology in Alzheimer's disease.