Alzheimer's (AD) patients show neuropathological changes in areas of the brain central to olfactory processing, suggesting the theoretical importance and potential diagnostic utility of investigating functional changes in olfaction in these patients. Persons with Down's Syndrome who live to the fourth decade develop neuropathological changes in the brain similar to those found in AD. A series of investigations have been conducted to assess olfaction function in both patients with Alzheimer's disease and persons with Down's Syndrome. Functional testing included olfactory threshold, odor identification, odor similarity judgements, odor recognition memory, odor recall, odor fluency. Both Alzheimer's patients and persons with Down's Syndrome showed significant impairment in olfactory function, with some measures showing more impairment than others in the early stages of the disease process. Longitudinal investigation of several of the measures indicated decreased function over time consonant with falling DRS scores. Normal controls who tested positive for the APOE4 allele showed impaired odor identification compared to those who were allele negative. Patients with Huntington's Disease showed olfactory functional impairments, although the degree of impairment differed from the cortical dementias for some of these tasks. The sensitivity and specificity of these assessments will be discussed in relation to analogous assessments in other sensory modalities.