The apolipoprotein E epsilon4 allele is the most common risk factor for Alzheimer's disease (AD). The epsilon2 allele may play a protective role in AD. Our previous cross-sectional study showed that in non-demented elderly subjects the epsilon2 allele is associated with better learning ability than other alleles. We wished to investigate the influence of different apolipoprotein E (apoE) phenotypes on cognitive functions in a 3-year follow-up study starting with a random sample of 917 non demented elderly subjects. Episodic memory was examined with the List Learning Test (Buschke's selective reminding method), as well as with immediate and delayed recall of figures. Retrieval from semantic memory was assessed with the Category and Verbal Fluency tests. Constructional abilities were examined by copying figures. Attention functions were examined with the Trail Making A and B tests. A total of 632 subjects completed the 3-year follow-up study. The subjects with apoE phenotypes E2/2 or E2/3 were able to maintain their verbal learning performance, while the learning ability of the subjects with other apoE phenotypes deteriorated. We suggest that successful mental aging may be at least in part associated with genetic factors.