Polyclonal antibodies directed against substance P, somatostatin, neurotensin, cholecystokinin (CCK), leucine enkephalin, and vasoactive intestinal polypeptide (VIP) were employed to determine the immunoreactivities of neurites of senile plaques (SP) in Alzheimer's disease (AD). All of the antibodies labeled some neurites in some SP. The transmitter specificities of immunoreactive neurites tended to reflect the distribution of transmitter-associated fibers in normal tissue. This investigation also documented the presence of abnormal axons (as distinct from neurites within plaques) in the neuropil in brains of individuals with AD and in some aged controls. These findings suggest that a variety of transmitter systems are involved in the formation of neuropil abnormalities of SP. They also indicate that a greater number of neuronal systems are affected in AD than have been documented by neurochemical studies.