Alzheimer's disease (AD) patients with moderate dementia show losses in olfactory threshold, odor identification and odor memory. Sensitivity and specificity of olfactory testing is significant, with the greatest power of accurate diagnosis in the more cognitively loaded olfactory tasks. In patients with very mild AD or in patients at risk for the disease because of their mild cognitive impairment, losses are apparent for odor identification, odor recognition memory and odor threshold, with the best sensitivity in the identification task. Persons who are either heterozygous or homozygous for the epsilon 4 allele of apolipoprotein E (ApoE) have an increased risk of Alzheimer's disease, although they show no dementia in the preclinical period. Evidence of olfactory dysfunction in this population might be reflective of an incipient dementing process. We have recently examined olfactory function in a group of normal elderly persons who have undergone genetic testing for the Apoe4 allele. These individuals consisted of all normal control subjects at the University of California, San Diego (UCSD) Alzheimer's Disease Research Center (ADRC) who had undergone both the genetic testing and testing for olfactory function. All had been diagnosed as normal control participants by two different neurologists who applied the National Institute of Neurological Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINDS-ADRDA) criteria for dementia. Persons with a history of alcoholism, drug abuse, learning disability or neurologic or psychiatric illness (including depression) were excluded. In this population, persons with the Apoe4 allele showed significantly poorer odor identification than those without an epsilon 4 allele. Early appearance of olfactory deficits in the progression to AD in persons with the epsilon 4 allele suggests diagnostic utility in olfactory testing.