The mydriatic response to dilute tropicamide was studied in 25 Japanese patients with Alzheimer's disease (AD), 13 patients with non-AD neurological diseases (non-AD) and 11 normal elderly subjects (control). Although the changes in resting pupil diameter and area over baseline were significantly greater (p < 0.05) in AD patients than in non-AD patients and controls, there was considerable overlap between the three groups. The change in resting pupil area was significantly greater (p < 0.05) in AD patients homozygous for ApoE epsilon 4 than in AD patients heterozygous for or without this allele. Despite a limited sample size in the present study, our results indicate that the pupil dilation assay by tropicamide is not an effective diagnostic tool for AD, and it may be modulated by different gene dosage of ApoE epsilon 4.