Human memory is a complex neurocognitive process. By combining psychological and molecular genetics expertise, we examined the APOE epsilon 4 allele, a known risk factor for Alzheimer's disease, and the COMT Val 158 polymorphism, previously implicated in schizophrenia, for association with lowered memory functioning in healthy adults. To assess memory type we used a range of memory tests of both retrospective and prospective memory. Genotypes were determined using RFLP analysis and compared with mean memory scores using univariate ANOVAs. Despite a modest sample size (n = 197), our study found a significant effect of the APOE epsilon 4 polymorphism in prospective memory. Supporting our hypothesis, a significant difference was demonstrated between genotype groups for means of the Comprehensive Assessment of Prospective Memory total score (p = 0.036; epsilon 4 alleles = 1.99; all other alleles = 1.86). In addition, we demonstrate a significant interactive effect between the APOE epsilon 4 and COMT polymorphisms in semantic memory. This is the first study to investigate both APOE and COMT genotypes in relation to memory in non-pathological adults and provides important information regarding the effect of genetic determinants on human memory. (C) 2012 Elsevier B.V. All rights reserved.