The formation of polyglutamine aggregates occupies a central role in the pathophysiology of neurodegenerative diseases caused by expanded trinucleotide repeats encoding the amino acid glutamine. This chapter describes sensitive histological methods for detection of tissue sites that are capable of further recruitment of polyglutamine and for sites rich in polyglutamine defined immunohistochemically. These methods have been found to be applicable in a number of diseases and animal models of disease. Recruitment, which is a property of highly ordered, amyloid-like aggregates, is most commonly found in punctate sites, termed aggregation foci (AF), in the neuronal perikaryonal cytoplasm. As expected, these AF correspond to sites containing polyglutamine aggregates detected using the antibody 1C2. Interestingly, however, many of the latter sites, including most neuropil aggregates and neuronal intranuclear inclusions, exhibit a limited ability to support polyglutamine recruitment. Thus there is limited correlation between the distribution of polyglutamine aggregates and recruitment activity, suggesting functional heterogeneity among polyglutamine aggregates. These methods should prove useful in explaining the relationship between aggregation reactions, aggregate formation, and the development of symptomatic disease and should be adaptable to the study of other protein aggregation disorders.