We examined the distribution of the apolipoprotein E (APOE) polymorphism in two Caucasian populations of Alzheimer's disease (AD) patients referred to dementia clinics; one in Gerona, Spain (66 AD patients, 49 controls), and the other in Pittsburgh, Pa., USA (209 AD patients, 58 controls). The presence of the APOE*4 allele was a significant risk for developing AD in both cohorts: Gerona (odds ratio = 2.34, CI: 1.03-5.55) and Pittsburgh (odds ratio = 3.64, CI: 1.78-7.69). The proportion of AD with the APOE*4 allele was greater in the Pittsburgh cohort than in the Gerona cohort (p = 0.02). However, no statistical difference was noted between the two populations in nondemented controls (p = 0.41). These data emphasize the importance of geographical and ethnic variations in the study of APOE genotypes.