Apolipoprotein E e4 (APOEe4) allele has been associated with an increased risk for Alzheimer's disease (AD) in diverse populations. Few studies have been carried out in Hispano-Americans and results are inconclusive due to ethnic diversity. This study determined the frequency of APOE alleles in a group of 61 Caucasian-Mestizos patients with probable AD, and 61 age- and sex-matched controls. APOEe4 frequency was 36.8% for patients, and 8.2% for controls (P < 0.0001; OR 7.6). Genotype frequencies differ between the two groups (P < 0.0001). Genotype 3/3 was the most common. Frequency of genotypes 3/4, 4/4 and 2/4 were higher in patients than in the controls. Our results show a highly significant association of APOEe4 with AD, and implies the importance of APOEe4 as a risk factor in this population.